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Vitamin D and atherosclerosis
Abstract
Purpose of review:
To provide an overview of the association between vitamin D deficiency and atherosclerosis.
Recent findings:
Vitamin D exerts protective effects on atherosclerosis through multiple mechanisms. It has been shown to protect against endothelial dysfunction, vascular smooth muscle cell proliferation and migration, and modulation of the immune system, as well as the inflammatory response. In addition, vitamin D has been shown to have systemic effects on insulin resistance, dyslipidemia, and hypertension.
Summary:
Vitamin D deficiency is widely prevalent in the United States and worldwide. Although deficiency of this fat-soluble vitamin is usually associated with musculoskeletal disorder, it is associated with a wide range of disease processes that include multiple organ systems. Recently, there has been mounting evidence linking vitamin D deficiency to cardiovascular disease and atherosclerosis.
... Several studies investigating the physiological and pathophysiological properties of the cardiovascular and cerebrovascular system have focused on the role of endothelial function in the maintenance of vascular health. Endothelial dysfunction, characterized by imbalanced vasodilation and vasoconstriction, elevated reactive oxygen species, and proinflammatory factors, decreases nitric oxide bioavailability and contributes significantly to the development and progression of cardiovascular and cerebrovascular diseases [15][16][17]. Although many mechanisms and risk factors of cardiovascular disorders have already been identified, the prevention and treatment strategies of vascular diseases are yet to be improved. ...
... The clinical manifestations of VitD toxicity are related primarily to hypercalcemia, and they include confusion, depression, psychosis, gastrointestinal disorders, renal failure, and cardiovascular symptoms, such as hypertension and bradyarrhythmia [39]. Surprisingly, it appears that both low and high 25(OH)D levels are associated with increased risk of total [40] and cardiovascular mortality [16,41], implying a Ushaped association between VitD concentrations and health. Although VitD appears to have a broad therapeutic window, the latter still has to be defined, especially for preventing cardiovascular and cerebrovascular diseases [31]. ...
... Further, VDD has been reported to decrease the lumen and increase the wall thickness of coronary arterioles of female rats [56]. Altered VSMC migration and proliferation may be responsible for the vascular remodeling in VDD [16]. However, the literature is controversial regarding the effect of VitD treatment on VSMCs. ...
Deficiency in vitamin D (VitD), a lipid-soluble vitamin and steroid hormone, affects approximately 24% to 40% of the population of the Western world. In addition to its well-documented effects on the musculoskeletal system, VitD also contributes importantly to the promotion and preservation of cardiovascular health via modulating the immune and inflammatory functions and regulating cell proliferation and migration, endothelial function, renin expression, and extracellular matrix homeostasis. This brief overview focuses on the cardiovascular and cerebrovascular effects of VitD and the cellular, molecular, and functional changes that occur in the circulatory system in VitD deficiency (VDD). It explores the links among VDD and adverse vascular remodeling, endothelial dysfunction, vascular inflammation, and increased risk for cardiovascular and cerebrovascular diseases. Improved understanding of the complex role of VDD in the pathogenesis of atherosclerotic cardiovascular diseases, stroke, and vascular cognitive impairment is crucial for all cardiologists, dietitians, and geriatricians, as VDD presents an easy target for intervention.
... Nitric oxide, mentioned previously, serves a protective function in the endothelium. Interestingly, vitamin D increases endothelial nitric oxide thereby helping to maintain the vasculature and avoid atherosclerosis (Menezes et al., 2014). Vitamin D deficiency is common globally and seems to be implicated in several stages in the pathophysiology of atherosclerosis (Kassi et al., 2013;Latic and Erben, 2020). ...
... However, it is unclear whether vitamin D regulates mitochondrial dysfunction in atherosclerosis development (Mandarino et al., 2015;Poznyak et al., 2021). Moreover, VDR being found on various tissue types, including brain and pancreas tissue, links vitamin D and cardiovascular diseases such as atherosclerosis and hypertension stronger (Menezes et al., 2014). In addition to the direct relationship between vitamin D deficiency and heart disease, the deficiency can indirectly exacerbate cardiac symptoms by interfering with endocrine processes that impact cardiac function. ...
... In addition to the direct relationship between vitamin D deficiency and heart disease, the deficiency can indirectly exacerbate cardiac symptoms by interfering with endocrine processes that impact cardiac function. One example of this indirect link is the ability of vitamin D to decrease insulin resistance, which ultimately benefits patients with atherosclerosis and hypertension by decreasing the activity of lipoprotein lipase, leading to a decrease in the level of lipoproteins and LDLs in the blood (Menezes et al., 2014). ...
Vitamin D, a secosteroid hormone, appears to have significant beneficial effects on various physiological systems, including the musculoskeletal system. Vitamin D assists in the regulation of numerous critical biological functions and physiological processes in humans, including inflammation, oxidative stress, and mitochondrial respiration, and is also linked to cardiac diseases. It is also reported that vitamin D plays a central role in molecular and cellular mechanisms, which reduce oxidative stress, and tissue damage and regulate cellular health. On the other side, hypovitaminosis D reduces mitochondrial activity and increases oxidative stress and inflammation in the body. Hypervitaminosis D increases the prevalence and severity of cellular damage. It has also been reported that vitamin D is involved in many functions of the reproductive system in human and critically play an important role in the reproductive tissues of women and men. Its role is very well defined, starting from female menarche to menopause, 968 pregnancy, and lactation, and finally in male fertility. Hence, the appropriate amount of vitamin D is necessary to maintain the normal function of cell organelles. Based on recent studies, it is understood that vitamin D is involved in the biological activities of mitochondria in cells, especially in cardiomyocytes. In this review, we emphasized the role of vitamin D in mitochondrial respiration, which could significantly influence heart health and human reproduction.
... Vitamin D is cardioprotective, it is involved in different pathways that lower the risk of atherosclerosis(Abu el Maaty and Gad 2013; Kienreich et al. 2013;Menezes et al. 2014). ...
... inflammation while T-helper 2(Th2) are anti-atherogenic through the secretion of IL-5, IL-10, IL-13. Vitamin D acts through shifting the immune response towards the effect of Th2 away from Th1 (Kassi et al. 2013).Vitamin D decreases the expression of renin, thus lowers blood pressure (Kienreich et al. 2013).It has anti-inflammatory action through decreasing the activity of NF-κB (Menezes et al. 2014)and increasing the expression of endothelial nitric oxide synthase(eNOS) (Abu el Maaty and Gad 2013). The increase in NO is very beneficial as it is a potent vasodilator and inhibitor of platelet aggregation (Menezes et al. 2014).A case-control study was conducted on New Zealand population showed that myocardial infarction is inversely associated with the level of 25-hydroxy vitamin D 3 (Scragg et al. 1990). ...
... Vitamin D acts through shifting the immune response towards the effect of Th2 away from Th1 (Kassi et al. 2013).Vitamin D decreases the expression of renin, thus lowers blood pressure (Kienreich et al. 2013).It has anti-inflammatory action through decreasing the activity of NF-κB (Menezes et al. 2014)and increasing the expression of endothelial nitric oxide synthase(eNOS) (Abu el Maaty and Gad 2013). The increase in NO is very beneficial as it is a potent vasodilator and inhibitor of platelet aggregation (Menezes et al. 2014).A case-control study was conducted on New Zealand population showed that myocardial infarction is inversely associated with the level of 25-hydroxy vitamin D 3 (Scragg et al. 1990). Moreover, a retrospective analysis done by the Intermountain Heart Collaborative (IHC) Study Group showed that low levels of vitamin D were highly associated with coronary artery disease and myocardial infarction (Kassi et al. 2013). ...
Cardiovascular diseases remain a major public health burden worldwide. It was reported that vitamin D protects the cardiovascular system through several mechanisms mainly by hindering atherosclerosis development. Genetic variations in vitamin D metabolic pathway were found to affect vitamin D levels. This study aimed at investigating the association between single nucleotide polymorphisms in genes involved in vitamin D metabolism, CYP27B and CYP24A1; 25-hydroxyvitamin D (25(OH)D) levels; and susceptibility to acute coronary syndrome (ACS). One hundred and eighty-five patients and 138 healthy controls were recruited. CYP24A1 rs2762939 was genotyped using fast real-time PCR, while CYP24A1 rs4809960 and CYP27B1 rs703842 were genotyped using polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP). 25(OH)D3 and 25(OH)D2 levels were measured using ultra-performance liquid chromatography tandem mass spectrum. Vitamin D level was significantly lower in patients than controls (p < 0.05). The GG genotype of rs2762939 was significantly associated with the risk of ACS development, but not correlated to the vitamin D level. rs4809960 and rs703842 genetic variations were not associated with ACS nor with 25(OH)D level. The genetic variant rs2762939 of CYP24A1 is remarkably associated with ACS. Meanwhile, the variants rs4809960 and rs703842 are not associated with ACS incidence.
... [6] Loss of collagen and disruption of elastic lamellae are additional features. [136,137] These latter changes are usually associated with increased aortic stiffness [136] although one study reported a paradoxical reduction in stiffness. [138] Vitamin D also exacerbates the intimal hyperplasia seen in balloon-injured rat carotid arteries. ...
... [112,140,141] Recently, the combination of Vitamin D 2 and cholesterol has been used to induce both peripheral atherosclerosis and aortic valve stenosis in a rabbit model. [6,137,142] In this model, the addition of Vitamin D 2 to the high cholesterol diet resulted in significantly higher levels of circulating cholesterol. [142] A combination of Vitamin D and nicotine, causing hypercalcemia, results in stiffer rat conductance arteries and exacerbates the atherosclerotic effects of cholesterol feeding. ...
... [143] These rats had low levels of plasma 24, 25(OH) 2 D 3 ), and developed hyperlipidemia and aortic atherosclerosis. [137,143] This is an example of the complexity of the relationship between differing Vitamin D metabolites and the arterial wall. [6] Clinical Application of Vasculoprotective Effect of Vitamin D Clinical trials using Vitamin D as supplement produced inconsistent findings. ...
... In the present study we found that lowered levels of the key antioxidants zinc and vitamin D3 were inversely associated with ATS. As discussed in the introduction vitamin D deficiency may increase risk to ATS and cardio-vascular disease [22,[76][77][78][79]. Vitamin D may protect against ATS trough antioxidant, anti-inflammatory and anti-atherogenic effects as well as modulation of endothelial functions, IR, and vascular cell differentiation and growth [77,78]. ...
... In the present study we found that lowered levels of the key antioxidants zinc and vitamin D3 were inversely associated with ATS. As discussed in the introduction vitamin D deficiency may increase risk to ATS and cardio-vascular disease [22,[76][77][78][79]. Vitamin D may protect against ATS trough antioxidant, anti-inflammatory and anti-atherogenic effects as well as modulation of endothelial functions, IR, and vascular cell differentiation and growth [77,78]. Our findings on zinc extend those of previous papers reporting lowered serum zinc in ATS [80]. ...
Background
Aberrations in endothelial cells, immune and oxidative pathways are associated with atherosclerosis (ATS) and unstable angina (UA). The role of trace elements, minerals, and the endogenous opioid system (EOS) in UA are less well established.
Methods
We measured lipid, insulin resistance (IR), and immune, trace element (copper and zinc), mineral (magnesium, calcium), EOS (β-endorphin and mu-opioid receptor (MOR)) and antioxidant (vitamin D3) biomarkers in patients with ATS (n = 60) and UA (n = 60) and healthy controls (n = 58).
Results
ATS patients showed increased atherogenic and IR indices, IL-6, IL-10, β-endorphin, copper and magnesium, and lower zinc than healthy controls. Logistic regression showed that UA was significantly discriminated from ATS without UA with an accuracy of 85.5 % using calcium, IL-10, β-endorphin, MOR, triglycerides, IR (all positively), and copper and vitamin D3 (inversely). Neural networks showed that UA was discriminated from ATS without UA with an area under the ROC curve of 0.942 using MOR, β-endorphin, calcium, insulin resistance, vitamin D3 and copper as input variables. We found that 50.0 % of the variance in IR was explained by the regression on copper, IL-10, IL-6 (all positively), and zinc (inversely), while 32.9 % of the variance in the atherogenic index of plasma was explained by copper, IL-10 (both positively), and magnesium (inversely).
Conclusion
UA is not only mediated by insulin resistance, atherogenicity, and immune disorders, but also by aberrations in the endogenous opioid system and trace elements as well as lowered antioxidant levels. Copper appears to play a key role in IR and atherogenicity.
... In the present study we found that lowered levels of the key antioxidants zinc and vitamin D3 were inversely associated with ATS. As discussed in the introduction vitamin D deficiency may increase risk to ATS and cardio-vascular disease [22,[75][76][77][78]. Vitamin D may protect against ATS trough antioxidant, anti-inflammatory and anti-atherogenic effects as well as modulation of endothelial functions, IR, and vascular cell differentiation and growth [76,77]. ...
... In the present study we found that lowered levels of the key antioxidants zinc and vitamin D3 were inversely associated with ATS. As discussed in the introduction vitamin D deficiency may increase risk to ATS and cardio-vascular disease [22,[75][76][77][78]. Vitamin D may protect against ATS trough antioxidant, anti-inflammatory and anti-atherogenic effects as well as modulation of endothelial functions, IR, and vascular cell differentiation and growth [76,77]. Our findings on zinc extend those of previous papers reporting lowered serum zinc in ATS [79]. ...
Background: Aberrations in endothelial cells, immune and oxidative pathways are associated with atherosclerosis (ATS) and unstable angina (UA). The role of trace elements, minerals, and the endogenous opioid system (EOS) in UA are less well established. Methods: We measured lipid, insulin resistance (IR), and immune, trace element (copper and zinc), mineral (magnesium, calcium), EOS (β-endorphin and mu-opioid receptor (MOR)) and antioxidant (vitamin D3) biomarkers in patients with ATS (n=60) and UA (n=60) and healthy controls (n=58). Results: ATS patients showed increased atherogenic and IR indices, IL-6, IL-10, β-endorphin, copper and magnesium, and lower zinc than healthy controls. Logistic regression showed that UA was significantly discriminated from ATS without UA with an accuracy of 85.5% using calcium, IL-10, β-endorphin, MOR, triglycerides, IR (all positively), and copper and vitamin D3 (inversely). Neural networks showed that UA was discriminated from ATS without UA with an area under the ROC curve of 0.942 using MOR, β-endorphin, calcium, insulin resistance, vitamin D3 and copper as input variables. We found that 50.0% of the variance in IR was explained by the regression on copper, IL-10, IL-6 (all positively), and zinc (inversely), while 32.9% of the variance in the atherogenic index of plasma was explained by copper, IL-10 (both positively), and magnesium (inversely). Conclusion: UA is not only mediated by insulin resistance, atherogenicity, and immune disorders, but also by aberrations in the endogenous opioid system and trace elements as well as lowered antioxidant levels. Copper appears to play a key role in IR and atherogenicity.
... In the present study we found that lowered levels of the key antioxidants zinc and vitamin D3 were inversely associated with ATS. As discussed in the introduction vitamin D deficiency may increase risk to ATS and cardio-vascular disease [22,[75][76][77][78]. Vitamin D may protect against ATS trough antioxidant, anti-inflammatory and anti-atherogenic effects as well as modulation of endothelial functions, IR, and vascular cell differentiation and growth [76,77]. ...
... In the present study we found that lowered levels of the key antioxidants zinc and vitamin D3 were inversely associated with ATS. As discussed in the introduction vitamin D deficiency may increase risk to ATS and cardio-vascular disease [22,[75][76][77][78]. Vitamin D may protect against ATS trough antioxidant, anti-inflammatory and anti-atherogenic effects as well as modulation of endothelial functions, IR, and vascular cell differentiation and growth [76,77]. Our findings on zinc extend those of previous papers reporting lowered serum zinc in ATS [79]. ...
Background. Aberrations in endothelial cells, immune and oxidative pathways are associated with atherosclerosis (ATS) and unstable angina (UA). The role of trace elements, minerals, and the endogenous opioid system (EOS) in UA are less well established.
Methods. We measured lipid, insulin resistance (IR), and immune, trace element (copper and zinc), mineral (magnesium, calcium), EOS (β-endorphin and mu-opioid receptor (MOR)) and antioxidant (vitamin D3) biomarkers in patients with ATS (n=60) and UA (n=60) and healthy controls (n=58).
Results. ATS patients showed increased atherogenic and IR indices, IL-6, IL-10, β-endorphin, copper and magnesium, and lower zinc than healthy controls. Logistic regression showed that UA was significantly discriminated from ATS without UA with an accuracy of 85.5% using calcium, IL-10, β-endorphin, MOR, triglycerides, IR (all positively), and copper and vitamin D3 (inversely). Neural networks showed that UA was discriminated from ATS without UA with an area under the ROC curve of 0.942 using MOR, β-endorphin, calcium, insulin resistance, vitamin D3 and copper as input variables. We found that 50.0% of the variance in IR was explained by the regression on copper, IL-10, IL-6 (all positively), and zinc (inversely), while 32.9% of the variance in the atherogenic index of plasma was explained by copper, IL-10 (both positively), and magnesium (inversely).
Conclusion. UA is not only mediated by insulin resistance, atherogenicity, and immune disorders, but also by aberrations in the endogenous opioid system and trace elements as well as lowered antioxidant levels. Copper appears to play a key role in IR and atherogenicity.
... Nonetheless, the metabolisms of a vitamin D was started through theUV B radiation at a wavelength (290- 315 nm) exposure to human cutaneous, it converts 7-dehydrocholesterol and obtained (pre-vitamin D 3 (Holick, 2006;Holick, 2007;Menezes et al, 2014). Synthesis and metabolism of vitamin D are shown in (Fig. 1). ...
... A report study was postulated that vitamin D has several impacts mechanism on atherosclerosis or (coronary artery disease). The maintenance role of vitamin D on atherosclerosis included elevates endothelial nitric oxide (NO), prevents platelet and leukocyte aggregation and adhesion, declines in endothelial oxidative stress, influences vascular muscle tone and also has significant role in prevents proliferation and migration of vascular smooth muscle cells (Menezes et al, 2014). However, some research study has been predicted that coronary atherosclerosis,composition and burden of coronary plaque has been associated with the lack in 25(OH)D (Satilmis et al, 2015). ...
Increase in the lack of vitamin D in patients with atherosclerosis is risk factor for CVD health. This work, evaluate the impacts of vitamin D deficiency in cardiovascular disease patients as an important objective and determine the relationship between serum vitamin D with blood glucose, cholesterol (CH), triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), alkaline phosphate (ALP), alanine transaminase (ALT), aspartate transaminase (AST), albumin, total-protein (T-protein), total-bilirubin (T-bilirubin), blood urea, creatinine, calcium (Ca 2+), sodium (Na +), potassium (K +), phosphate (PO 4 3-), Troponin and CK-MB. In this study 102 subjects wereconducted (39 women and 63 men), they were undergoing elective urgent coronary angiography who had (diameter stenosis < %50) as a patients group, and 45 healthy subjects (20 women and 25 men) were conducted as a control group.The biochemical parameters of serum total 25(OH) D, Troponin-hs and CK-MB were measured via fully automated analyzer Cobas e 411 diagnostic kits (Roche/Hitachi Cobas) of German origin. The parameters of serum blood glucose, CH, TG, LDL, HDL, VLDL, creatinine and urea measured by using fully automated chemical analyzer of Cobas c 311 with diagnostic kits (Roche/Hitachi Cobas), of German origin. The parameters of electrolytes Ca 2+ , K + , Na + and PO 4 3-measured via fully automated 9180 Electrolyte Analyzer. Blood samples were taken from both patients and control group, who were aged < 40 years old. The results of this study revealed that the mean levels of total vitamin D are significantly lower in patients group with CVD rather than in control group. Whereas, the mean levels of blood glucose, CH, TG, LDL, VLDL, ALP, ALT, AST, T-bilirubin, blood urea and creatinine are significantly increased in patients group with CVD rather than control group.While, the mean levels of HDL, albumin and T-protein are significantly decreased in patients group with CVD when compared to control group. The results display that mean levels of Ca 2+ , PO 4 3-, K + and Na + are significantly decreased in patients group with CVD rather than control group. The mean levels of cardiac biomarker Troponin and CK-MB are significantly increased in patients group with CVD than those in control group. In a correlation analysis, the results display no significant correlations among total vitamin D with blood glucose, CH, TG, HDL and VLDL, ALP, ALT, AST, albumin, T-bilirubin, T-protein, blood urea, creatinine, PO 4 3-, Na + and Troponin. While, there are significant correlations between total vitamin D with LDL, Ca 2+ , K + and CK-MB. These findings reveal that serum vitamin D and serum blood glucose could be used as biomarkers for the diagnostic accuracy of CVD in men and women. These data demonstrate that serum CK-MB and serum Troponin are indeed potential biomarkers for CVD, due to the high levels of area under the curve (AUC).
... [9] Vitamin D deficiency is also shown to affect the progression of atherosclerosis. [10] Vitamin D is a steroid hormone whose main function is to regulate the balance of calcium and phosphorus metabolism by acting on parathyroid glands, kidneys, and intestines. Although vitamin D can be ingested through food, it mainly comes from the synthesis of human body in vivo. ...
... [30] In recent years, the research on the maintenance of human health on the role of vitamin D increases, more and more evidence that vitamin D is not only a significant benefit for the prevention of osteoporosis and fractures, and may reduce the risk of cancer, infection, autoimmune diseases, cardiovascular system, and nervous system disease incidence rate. [7,10] At present, vitamin D has neuroprotective effects, which can control the proinflammatory cytokines inducing cognitive impairment, participate in the synthesis of acetylcholine in neurotransmitters, [31,32] and also relate to atherosclerosis, cerebral infarction, diabetes and hypertension. [11] The complex mechanism of intracellular vitamin D has been established. ...
Lower circulating vitamin D is common in older adults and may be a potential reversible risk factor for cardiovascular disease (CVD) in older adults, however, presented controversial results.Database was searched update to February 2018. Key data were extracted from eligible studies. Dose-response meta-analysis were conducted for synthesizing data from eligible studies.A total of 13 eligible studies involving 21,079 participants were included in this meta-analysis. Person with lower 25-hydroxyvitamin D status (25 (OH)D level <50 nmol/L) appeared to have higher mortality of CVD in older adults (RR = 1.54, 95% CI 1.24-1.91). Furthermore, a significantly higher mortality of CVD in older adults was observed for the deficient (<25 nmol/L; RR = 1.47, 95% CI 1.15-1.81) and insufficient (25-50 nmol/L; RR = 1.16, 95% CI 1.04-1.27) categories of 25 (OH)D, compared to the reference category of >75 nmol/L. Additionally, decrease of 10 nmol/L 25-hydroxyvitamin D was associated with a 7% incremental in the risk of CVD mortality in older adults.Considering these promising results, circulating vitamin D is associated with CVD mortality increment in older adults.
... Other than vitamins C and E, vitamins A and D show potential antiatherosclerotic properties (as reviewed by [136]). The wide range of vitamin D beneficial functions includes reduction of endothelial dysfunction and VSMC proliferation and migration, as well as downregulation of the atherosclerosis-related inflammatory and immune processes [136]. ...
... Other than vitamins C and E, vitamins A and D show potential antiatherosclerotic properties (as reviewed by [136]). The wide range of vitamin D beneficial functions includes reduction of endothelial dysfunction and VSMC proliferation and migration, as well as downregulation of the atherosclerosis-related inflammatory and immune processes [136]. Less is known about vitamin A (retinol) in this context: retinoic acid (RA) metabolites, derivatives of vitamin A, limit VSMC growth, differentiation, and proliferation [137] and prevent high-fat diet-(HFD-) induced atherogenesis in ApoE -/mice via the upregulation of aforementioned transporters ABC-A1 and ABC-G1 [138]. ...
Despite the currently available pharmacotherapies, today, thirty percent of worldwide deaths are due to cardiovascular diseases (CVDs), whose primary cause is atherosclerosis, an inflammatory disorder characterized by the buildup of lipid deposits on the inside of arteries. Multiple cellular signaling pathways have been shown to be involved in the processes underlying atherosclerosis, and evidence has been accumulating for the crucial role of Notch receptors in regulating the functions of the diverse cell types involved in atherosclerosis onset and progression. Several classes of nutraceuticals have potential benefits for the prevention and treatment of atherosclerosis and CVDs, some of which could in part be due to their ability to modulate the Notch pathway. In this review, we summarize the current state of knowledge on the role of Notch in vascular health and its modulation by nutraceuticals for the prevention of atherosclerosis and/or treatment of related CVDs.
... В результате любое повреждение этого слоя сосудистой стенки может привести к эндотелиальной дисфункции, которая в конечном итоге играет ключевую роль в развитии атеросклероза. Защитная роль витамина D в снижении частоты риска развития атеросклероза заключается в [8]: ...
... Полученные данные имеют важное значение для общественного здравоохранения, учитывая высокую распространенность дефицита витамина D. Необходимо принимать во внимание и тот факт, что пациенты, страдающие гипертонической болезнью, ишемической болезнью сердца, ХСН, как правило, люди не всегда мобильные, вынуждены вести малоподвижный образ жизни, реже выходят из дому, мало бывают на солнце, поэтому у них вполне может развиться недостаток витамина D. Проспективные наблюдения показывают, что низкие концентрации витамина D связаны с повышенным риском развития сердечно-сосудистых заболеваний, смертности от них и смертности от всех причин [2,8,52,53]. ...
Vitamin D deficiency is widespread worldwide and present in about 30-50% of population. In most cases, this problem is associated with musculoskeletal system pathology: rickets in children, and osteomalacia or osteoporosis in adults. However, in recent years, convincing data was obtained on the links between vitamin D deficiency and cardiovascular pathology. Low Vitamin D levels in humans are associated with the unfavorable cardiovascular risk factors, such as arterial hypertension (AH), diabetes mellitus, and dyslipidemia, which are the predictors of the severe cardiovascular diseases, including strokes and infarctions. It has been demonstrated that vitamin D has a strong vasoptotective effect via endothelial dysfunction improvement, prevents blood vessels and myocardium remodeling, improves blood pressure parameters, reduces the risk of development of left ventricular hypertrophy, slows down fibrosis, reduces the risk of atherosclerosis, reduces insulin resistance, and also affects inflammation and immunity. This article provides data of Russian and foreign studies demonstrating the effect of Vitamin D deficiency on the development of atherosclerosis, AH, heart rhythm disorder and progression of chronic heart failure.
... Statins √ Decrease several molecules associated with atherosclerosis: IL6, TNFα, IFNγ, IL8, Pselectin (153,154) χ Treatment with statins did not show a significant effect in cIMT and plaque development (155,156) √ Decrease of plasma levels of MCP1, highsensitivity CRP, and trombomodulin (157,158) √ Atorvastatin possibly reduces carotidfemoral PWV (159) ACEIs/ARBs χ The cumulative occurrence of CVE was not shown to be statistically significant in lupus nephritis patients treated with ACEIs/ARBs (160) √ ACEI nonuse has been associated with carotid plaque area (161) Aspirin χ No effects on atherosclerosis biomarkers, such as homocysteine, highsensitivity CRP, soluble vascular cell adhesion molecule 1, Pselectin, and thrombomodulin (158) √ The association with HCQ has synergistic thromboprotective effect (162,163) √ Reduces CVE in aPL positive patients (164) HCQ √ Prevents the development of endothelial dysfunction via reduction of reactive oxygen species (165) √ Favorable effects on lipid and glycemic control (166,167) √ Reduces the risk of thrombovascular events (162,163,169,170) √ Is associated with lower progression of carotid plaque and aortic stiffness (170) √ Inhibits platelet aggregation and activation mediated by aPL (168) MMF √ Reduces proinflammatory and metalloproteinase genes expression (171) χ No clear effect on progression of cIMT or coronary calcification (172) √ Inhibits CD4+ Tcell activation and infiltration to atherosclerotic lesions (173) Azathioprine χ Linked to higher risk of CVE (40,138,174,175) Cyclophosphamide √ Has been associated with a lower prevalence of abnormal aortic IMT and plaques (123) Cyclosporine A √ Possibly protective against increased cIMT (148) Antibodies against BAFFR √ Reduce atherosclerosis in mice (176) √ Depletes B2 cells subtype and preserves B1 cells subtype (176)(177)(178) √ Prevents thrombosis in antiphospholipid syndrome (179) CD20specific monoclonal antibodies √ Significantly decreased atherosclerosis in mice (180) √ Reduce the IgG type antiOxLDL antibodies and the accumulation of Bcells, macrophage, and Tlymphocytes in atherosclerotic plaques (180) Vitamin D √ Decreases the production of proinflammatory chemokines and the quantity of inflammatory effector cells in atherosclerotic plaques (181) √ Vitamin D deficiency hampers vascular repair and reduces endothelial disfunction (186) √ Vitamin D deficiency increases expression of type I IFN (186) χ No protective effect of supplementation in atherosclerosis has been showed in SLE, despite that vitamin D deficiency has been linked to premature atherosclerosis (96)(97)(98)(182)(183)(184)(185) plaque burden and aortic stiffness in SLE patients (170). One recent paper from Fasano and colleagues supported the association of HCQ and aspirin in patients with Lupus for primary prevention of CVE (162). ...
... Vitamin D regulates several important immune functions and its deficiency has been linked to premature atherosclerosis (182)(183)(184)(185). In apolipoprotein E knockout mice, calcitriol treatment changes the function or differentiation of dendritic cells and regulatory T-cells, decreases the production of pro-inflammatory chemokines, and reduces the quantity of inflammatory effector cells in atherosclerotic plaques (181). ...
IntroductionThe systemic inflammatory nature of systemic lupus erythematosus (SLE) is well patent not only in the diverse clinical manifestations of the disease but also in the increased risk of premature atherosclerosis and cardiovascular events (CVE), making SLE one of the most complex diseases to study and manage in clinical practice.AimTo travel from old aspects to modern insights on the physiopathology, new molecular biomarkers, imaging methods of atherosclerosis assessment, and the potential treatments of atherosclerosis in SLE.Methods
We conducted a literature search using PubMed database and performed a critical review.Conclusion/discussionSeveral developments have taken place in the understanding of the relationship between SLE and premature atherosclerosis. Nevertheless, cardiovascular diseases are still the major cause of reduced life expectancy in SLE and the main cause of death. The lack of standardization methods for the imaging assessment of atherosclerosis in SLE and the multifactorial nature of the disease are well patriated in the difficulty of achieving consistent and reproducible results among studies that focus in cardiovascular risk assessment and prediction. A raising number of molecular biomarkers of atherosclerosis have been proposed, but the combination of several biomarkers and risk factors may better estimate cardiovascular disease risk. Moreover, the development of effective therapies to prevent progression of atherosclerosis and CVE shall address systemic inflammation.
... 23,35, 36 Administration vitamin D3 can suppress renin and angiotensin gene expression by inhibiting the NFκB pathway. 23, 35 Vitamin D3 also exhibits vasoprotective effects by improving endothelial function, inhibiting VSMC proliferation and down-regulating inflammatory processes. 35,36 Vitamin D3 is believed to affect the function of macrophages which are very crucial in the formation of foam cells. ...
Background: Increased blood pressure that occurs in chronic kidney disease (CKD) is influenced by the occurrence of thickening of blood vessels. This study evaluates the utilization of propolis which acts as an anti-inflammatory and vitamin D3 which plays a role in calcium-phosphate metabolism, that when combined are expected to prevent atherosclerosis. Methods: This experimental research used a post-test only group design with a total of 24 male rats divided into 3 groups. Subjects were induced to develop CKD with unilateral ureteral obstruction. A combination of 50mg/kgBW of propolis and 0.126mcg/kgBW of vitamin D3 was given orally every morning in the intervention group. Hemodynamics and atherosclerosis status were observed using sonography until week 4. Inflammatory markers with vascular cell adhesion molecule 1 (VCAM-1) and Caspase-3 were evaluated weekly via plasma and target organ samples were immunohistochemically examined at the study’s end. Results: Propolis and vitamin D3 significantly reduced blood pressure from 156 mmHg at the beginning of the study to 117mmHg at week 4 (p=0.000). Thickening of the aorta occurred in the control and intervention groups but the thickening in the control group (0.90mm) was statistically significantly (p=0.000) higher than the intervention group (0.30mm). There were decreased VCAM-1 and Caspase-3 levels in the intervention group compared to the control group, both in plasma and target organ levels Conclusion: Utilization of propolis and vitamin D3 combined has a good effect on lowering inflammation, improving hemodynamics and preventing atherosclerosis in chronic kidney disease rat models.
... Yüksek plazma ADMA konsantrasyonunun NO üretimini azaltarak endotelyal disfonksiyon, aterosklerozun ilerlemesine ve kardiyovasküler olaylara yol açtığı gösterilmiştir [5]. 25-OH Vitamin D'nin ise endotelyal disfonksiyon ve VDKH proliferasyonu, migrasyonunu önleyici etkisi ile aterosklerozdan koruyucu olduğu gösterilmiştir [6]. Bu çalışmada aynı hasta grubunda tıkayıcı koroner arter hastalığı ile 25OH-vitamin D, MGP, Fetuin-A, ADMA düzeyleri arasındaki ilişki değerlendirilerek erken teşhis, gereksiz girişimsel işlemlerinden kaçınılması ve yüksek risk gruplarında hızlı tedavi güvenilirliği değerlendirilmiştir. ...
In this study, the relationship between the markers of 25OH-vitamin D, Matrix Gla Protein (MGP), Fetuin-A, Asymmetric Dimethyl Arginine (ADMA), which are suggested to play a role in the etiology of atherosclerosis, and coronary artery disease was investigated. For this purpose, a total of 80 patients, including 40 patients with normal coronary artery and 40 patients with 70% or more stenosis in at least one coronary artery, who underwent coronary angiography with a preliminary diagnosis of coronary artery disease, were included in the study. While blood MGP levels were observed to be significantly higher in the coronary artery disease group compared to the control group (2082.79±329.75 pg/ml and 1853.42±285.82 pg/ml, p=0.001, respectively), Fetuin-A levels in the control group group was significantly lower than the coronary artery disease group (60.54±28.61 ng/ml and 78.61±20.45 ng/ml, respectively, p=0.002). Although 25OH-vitamin D levels were observed at low levels in 85% of the patients in both groups, no statistically significant difference was found between the two groups (20.27±12.65 ng/ml and 20.64±7.32 ng/ml, respectively). ml, p=0.875). When blood ADMA levels were examined, no statistically significant difference was observed between the groups (group 1; 0.099±0.053 umol/l and group 2; 0.089±0.051 umol/l, p>0.05). As a result; While no significant relationship was found between 25OH-vitamin D and ADMA values and coronary artery disease, it was observed that MGP and Fetuin-A could be markers for occlusive coronary artery disease. In our study, it was observed that MGP and Fetuin-A biomarkers were guiding in the diagnosis of occlusive coronary artery disease. In the light of these findings, new studies with a similar background and larger populations are needed to evaluate the use of MGP and Fetuin-A levels in the diagnosis of coronary artery disease.
... Supplementazione di vitamina D nella sindrome metabolica La supplementazione di vitamina D ha mostrato di avere effetti favorevoli nel trattamento di diverse condizioni associate alla sindrome metabolica, come la dislipidemia, l'insulino-resistenza, il DM2, l'ipertensione arteriosa e l'obesità [19,66] . I suddetti effetti potrebbero es-sere legati all'azione favorevole della vitamina D su diversi parametri fisiologici, tra cui la riduzione della rigidità arteriosa (arterial stiffness), la ridotta attivazione del sistema renina-angiotensina-aldosterone (SRAA), la riduzione dei livelli di PTH, la ridotta produzione di citochine pro-infiammatorie, la riduzione dello stress ossidativo, della disfunzione endoteliale e della proliferazione e migrazione delle cellule muscolari lisce vascolari, la riduzione dell'aterogenesi, l'aumento dell'attività dell'enzima lipoprotein lipasi, nonchè l'aumento della fosforilazione ossidativa mitocondriale a livello del muscolo scheletrico [28,[67][68][69][70][71][72][73] . ...
LRIOG - La Rivista Italiana di Ostetrica e Ginecologia. Volume 2022, Issue 1 (March 1, 2022): 95-106. p-ISSN: 1724-6776. e-ISSN: 1824-0283. DOI: 10.53146/lriog1202162 [Article in Italian].
Metabolic syndrome is a complex disorder characterized by the co-occurrence of several known cardiovascular risk factors, including obesity, insulin resistance, atherogenic dyslipidemia and hypertension. As such, metabolic syndrome is associated with an increased risk of cardiovascular disease and type 2 diabetes mellitus. Of note, metabolic syndrome is defined by the presence of at least three of the following conditions: abdominal obesity (or central obesity), high blood pressure (≥130/≥85 mmHg), abnormal fasting plasma glucose (≥100 mg/dL), elevated serum triglycerides (≥150 mg/dL) and low high-density lipoprotein (HDL)-cholesterol level (<40 mg/dL in men, <50 mg/dL in women). Over the last years, the global prevalence of metabolic syndrome has progressively increased as a consequence of the increasing rates of overweight/obesity, population ageing, and lifestyle changes favoring sedentary behaviors, physical inactivity and unhealthy dietary habits. On the other hand, the global prevalence of vitamin D deficiency has concurrently increased. To date, vitamin D deficiency is regarded as a global pandemic afflicting more than one billion individuals across all age groups worldwide. Since growing evidence suggests that vitamin D exerts several pleiotropic extraskeletal actions beyond its well-established role in the regulation of bone homeostasis, researchers have proposed that vitamin D deficiency may be involved in the pathophysiology of metabolic syndrome. Therefore, this brief Report article aims to summarize the current scientific evidence regarding the possible causal relationship between vitamin D deficiency and metabolic syndrome, as well as the potential favorable effects of vitamin D supplementation for prevention and treatment of metabolic syndrome and its associated diseases.
... Although the mechanism of how vitamin D deficiency increased the all-cause mortality risk is not completely clear. Growing evidence has shown that vitamin D has an extensive noncalcemic pleiotropic function mediated by vitamin D receptor (VDR) (36), associated with suppression of the reninangiotensin system (37), anti-myocyte hypertrophy (38), atherosclerosis lowering (39,40) and anti-inflammation (41,42). The activation of VDR in cardiomyocytes and endothelial cells could regulate vascular tension and smooth muscle contractions, thus providing protective effect on endothelial dysfunction (43). ...
Objective
To assess the association between vitamin D status and all-cause mortality among type 2 diabetes patients.
Research Design and Methods
We prospectively followed 1,291 participants with type 2 diabetes aged 20–80 years during 2013–2018. Cox proportional hazard regression models were used to estimate the association between different vitamin D status and all-cause mortality risk among hospitalized patients with type 2 diabetes.
Results
During a median follow-up of 4.15 years (5,365 person-years in total), 61 cases of death were identified. Multivariable-adjusted hazard ratios (HRs) for all-cause mortality across the quartiles of baseline circulating 25-hydroxy vitamin D (25-OH vitamin D) were 2.70 [95% confidence interval (CI) 1.12–6.54], 1.00, 1.39 (95% CI 0.53–3.65), 2.31 (95% CI 0.96–5.54), respectively. Multivariable-adjusted HRs for all-cause mortality by different groups of baseline 25-OH vitamin D concentrations (<25, 25–49, 50–100, and ≥100 nmol/L) were 1.31 (95% CI 0.58–2.96), 0.94 (95% CI 0.47–1.87), 1.00, and 3.58 (95% CI 1.43–8.98), respectively.
Conclusions
Very low or high concentrations of vitamin D may be associated with a higher risk of all-cause mortality among patients with type 2 diabetes.
... Також вітамін D впливає на рецептори клітин ендотелію, кардіоміоцитів, гладких м'язових клітин судинної стінки. Наявність VDR в ендотелії кровоносних судин сприяє тому, що кальцитріол може впливати на констрикційні та дилатаційні процеси, тим самим регулювати просвіт та органний кровотік, а також впливати на функцію гладком'язових клітин судинної стінки [38,39]. Метаболіти вітаміну D мають здатність впливати на ренін-ангіотензин-альдостеронову систему шляхом зниження її активності та синтезу реніну [20]. ...
Мета дослідження – провести аналіз наукових публікацій, які висвітлюють стан забезпеченості вітаміном D та його взаємозв’язки з розвитком метаболічного синдрому в дітей підліткового віку.
Матеріали та методи. Проведено аналіз публікацій баз даних Web of Sciense, SpringerOpen, Structure (NCBI), HINARI, PudMed, Scopus, які описують стан забезпеченості вітаміном D дітей залежно від індексу маси тіла і його взаємозв’язки з показниками антропометрії, вуглеводного та ліпідного обмінів.
Результати дослідження та їх обговорення. Ожиріння та дефіцит вітаміну D сприяють зростанню розвитку критеріїв метаболічного синдрому в дітей підліткового віку. Важливими чинниками розвитку дефіциту вітаміну D та метаболічного синдрому є низький дохід на члена сім’ї, недостатнє вживання молока, харчових продуктів, збагачених вітаміном D, низька фізична активність, недостатнє перебування на відкритому повітрі, тривале проведення часу за комп’ютером, гаджетами. Забезпеченість вітаміном D у підлітків з ожирінням характеризується прямими кореляційними зв’язками з рівнем у сироватці крові ліпопротеїнів високої щільності та зворотними кореляційними зв’язками з окружністю талії, рівнем тригліцеридів, глікемії, артеріальної гіпертензії.
Висновки. Дефіцит вітаміну D пов’язаний із чинниками ризику метаболічного синдрому в дітей з ожирінням. Поширеність дефіциту вітаміну D серед дітей підліткового віку залежить від багатьох чинників, які вважаються такими, що відіграють важливу роль у підвищених ризиках розвитку метаболічного синдрому. Встановлення механізмів взаємозв’язку дефіциту вітаміну D з чинниками ризику метаболічного синдрому в дітей з ожирінням дозволять розробити нові підходи, направлені на зниження ризиків ожиріння, метаболічного синдрому та пов’язаних із ними серцево-судинних захворювань.
... 25 Vitamin D deficiency also accelerates the progression of atherosclerosis. 26 It has been indicated that most of the populations have lower levels of vitamin D, 27,28 which could be a potential reversible risk factor for CVD. 29 Moreover, low HDL-cholesterol, high serum total cholesterol (TC) , LDL-cholesterol, Apo B/Apo A1 ratio is associated with low serum 25(OH) D. 30,31 Moreover, Apo B100/ Apo A1 ratio indicates anti-atherogenic /pro-atherogenic lipoproteins balance and could be a reliable risk indicator of cardiovascular conditions when compared with lipid parameters. ...
Cardiovascular disease (CVD) is a leading cause of death around the world. According to the studies, apolipoproteins A1 and B100 play crucial role in CVD development and progression. Also, findings have indicated the positive role of vitamin D on these factors. Thus, we conducted the present meta-analysis of randomized controlled trials (RCTs) to demonstrate the impact of vitamin D supplementation on apolipoproteins A1 and B100 levels in adults. PubMed and Scopus databases and Google Scholar were searched up to 21 December 2020. Relevant articles were screened, extracted, and assessed for quality based on the Cochrane collaboration’s risk of bias tool. Data analysis conducted by random-effect model and expressed by standardized mean difference (SMD). The heterogeneity between studies was assessed by I-squared (I2) test. Subgroups and sensitivity Analyses were also conducted. Seven RCTs were identified investigating the impact of vitamin D on Apo A1 levels and six on Apo B100 levels. The findings showed the insignificant effect of vitamin D supplementation on Apo A1 (SMD=0.26 mg/dL; 95% confidence interval (CI), −0.10, 0.61; P= 0.155) and Apo B100 (standardized mean difference (SMD)=-0.06 mg/dL; 95% CI, −0.24, 0.12; P=0.530) in adults. There was a significant between-study heterogeneity in Apo A1 (I2=89.3%, P<0.001) and Apo B100 (I2=57.1%, P=0.030). However, significant increase in Apo A1 in daily dosage of vitamin D (SMD=0.56 mg/dL; 95% CI, 0.02, 1.11; P=0.044) and ≤12 weeks of supplementation duration (SMD=0.71 mg/dL; 95% CI, 0.08, 1.34; P=0.028) was observed. No significant effects of vitamin D on Apo A1 and Apo B100 levels after subgroup analysis by mean age, gender, study population, dosage and duration of study. Overall, daily vitamin D supplementation and ≤12 weeks of supplementation might have beneficial effects in increasing Apo A1 levels, however, future high-quality trials considering these a primary outcome are required.
... As a result of endothelial dysfunction, inflammatory reactions occur that can lead to smooth muscle proliferation, thrombogenesis and contribute to the development of atherosclerosis. Vitamin D plays a protective role and reduces the risk of atherosclerosis by: decreasing platelet adhesion and aggregation, decreasing oxidative stress, increasing NO production, suppressing the release of proinflammatory cytokines and inhibiting smooth muscle fiber proliferation [3]. ...
Vitamin D deficiency occurs in 30-50% of the world's population [1]. Vitamin D deficiency increases in proportion to distance from the equator, which explains the increased filtration of UV rays. [2]. It causes rickets, osteoporosis, osteomalacia, but also cardiovascular disease. The Russian and foreign studies presented in this review indicate that moderate and severe vitamin D deficiency is a risk factor for the development of cardiovascular diseases. [3].A decrease in vitamin D levels is a risk factor for cardiovascular pathology: arterial hypertension (AH), dyslipidemia, diabetes mellitus (DM), myocardial fibrosis and a predictor of adverse cardiovascular events - strokes and heart attacks. Vitamin D has a vasoprotective effect, reducing endothelial dysfunction, has a positive effect on blood pressure, reduces the risk of left ventricular hypertrophy and atherosclerosis, slows down vascular remodeling and myocardial fibrosis, reduces insulin resistance, and affects the course of inflammatory processes [4].
... Ischemia arises from lack of eNOS. The endothelial cells contain VDR which express 1-alpha-hydroxylase that enables the endothelial cells carry out the conversion of 25-OHD to 1,25 (OH)2D which controls the expression of NOS in endothelial cells, thereby enhancing the production of NO [41]. Thus, administration of vitamin D to BMD patients may alleviate ischemia which occurs in skeletal and cardiac muscles, especially in patients suffering from vitamin D deficiency. ...
The correlation between Becker muscular dystrophy (BMD) and vitamin D has long been known, since vitamin D controls bone turnover which occurs in this disease. Thus, vitamin D is beneficial to some extent to BMD patients due to the fact that it has long been known to play an important part in bone metabolism. According to recent studies which suggest association between vitamin D and multiple diseases involving multiple organs, vitamin D may alleviate the pathophysiology of BMD. This review focuses on the benefits of vitamin D to BMD patients through alleviation of the pathophysiology and complications of the disease. Keywords: Becker muscular dystrophy, Cardiomyopathy, Vitamin D
... Vitamin D has protective effects on atherosclerosis through numerous mechanisms. It protects against endothelial dysfunction, vascular smooth muscle cell proliferation and migration and immune system modification (Menezesa, 2014). Furthermore, In vitro studies revealed that vitamin D suppresses pro-inflammatory cytokines and increases anti-inflammatory cytokines . ...
Vitamin D is a steroid hormone. Our body can synthesize vitamin D upon exposure to sunlight unlike all other vitamins, or obtain it from fortified foods or dietary supplements.
Interesting aspects have been clarified lately about this vitamin metabolism in the living cell and its different physiological roles concerning mineral and bone homeostasis, cardiovascular function, renal diseases, cancer and immune system modulation.
This review summarizes the impact of vitamin D and vitamin D metabolites (25-hydroxy vitamin D [25(OH)D] and 1,25-dihydroxy vitamin D [1,25(OH)2D]) in the human body.
... NO is produced in humans through NO synthase (NOS), which has several different isoforms, and the endothelial form (eNOS) is the one present constitutively in the blood endothelial cells [54]. Through its actions on the vessels' endothelial cells, vitamin D increases the nitric oxide levels, which is known to be a vasodilator and platelet antiaggregant and reduces the level of reactive oxygen species released [55,56]. eNOS activity through its control of vascular constriction or dilatation is one of several ways that endothelial function manifests. ...
Vitamin D, a crucial hormone in the homeostasis and metabolism of calcium bone, has lately been found to produce effects on other physiological and pathological processes genomically and non-genomically, including the cardiovascular system. While lower baseline vitamin D levels have been correlated with atherogenic blood lipid profiles, 25(OH)D supplementation influences the levels of serum lipids in that it lowers the levels of total cholesterol, triglycerides, and LDL-cholesterol and increases the levels of HDL-cholesterol, all of which are known risk factors for cardiovascular disease. Vitamin D is also involved in the development of atherosclerosis at the site of the blood vessels. Deficiency of this vitamin has been found to increase adhesion molecules or endothelial activation and, at the same time, supplementation is linked to the lowering presence of adhesion surrogates. Vitamin D can also influence the vascular tone by increasing endothelial nitric oxide production, as seen in supplementation studies. Deficiency can lead, at the same time, to oxidative stress and an increase in inflammation as well as the expression of particular immune cells that play a pivotal role in the development of atherosclerosis in the intima of the blood vessels, i.e., monocytes and macrophages. Vitamin D is also involved in atherogenesis through inhibition of vascular smooth muscle cell proliferation. Furthermore, vitamin D deficiency is consistently associated with cardiovascular events, such as myocardial infarction, STEMI, NSTEMI, unstable angina, ischemic stroke, cardiovascular death, and increased mortality after acute stroke. Conversely, vitamin D supplementation does not seem to produce beneficial effects in cohorts with intermediate baseline vitamin D levels.
... Vitamin D deficiency is a global health problem and many adults and also infants have low vitamin D levels worldwide (10) . Vitamin D has protective effects on atherosclerosis by increasing nitric oxide levels and decreasing oxidative stress in endothelium and also by inhibiting the proliferation of smooth muscle cells in vessels; thus, vitamin D deficiency is suggested to be associated with increased risks of coronary artery disease (11) . In the present study, we analyzed the association of preoperative vitamin D levels with operative mortality in patients who underwent CABG surgery. ...
... Рекомендуется суточное потребление витамина D на уровне не менее 800 МЕ (A. Menezes и соавт., 2014) и омега-3-ПНЖК в рекомендованных возрастных дозах [78]. Данные последних 2 лет показывают, что у пациентов с сердечной кахексией низкий уровень поступления в организм незаменимых АК с разветвленной цепью связан с ухудшением прогноза ХСН (T. ...
The article provides an analytical review of the use of oral enteral nutrition (OEN, or sip feeding) as an adjuvant therapy and nutritional and metabolic support in various diseases and pathological conditions. Liquid and powdery sip feeds are currently becoming increasingly widespread due to their physiological nature and effectiveness in maintaining a nutritional status and eliminating nutritional deficiency in patients from different fields of medicine: oncology, musculoskeletal disorders, cardiovascular and pulmonary diseases (chronic obstructive pulmonary disease) and others. These sip mixtures contain proteins, fats, carbohydrates (macronutrients), omega-3 polyunsaturated fatty acids, as well as vitamins and minerals. Sip feeding is a supplement to a regular diet and is given between meals. The most prevalent sip feeding scheme is taking liquid forms of sip feeds in volumes of 200300 ml 23 times a day. Regimes which combine a regular diet and OEN should provide target indicators of energy and protein consumption: 2530 kcal/kg per day and 1.41.8 g of protein per 1 kg of body weight per day. In extremely severe cases, protein intake may be increased. Calorie ratio for individual nutrients in total energy consumption: proteins/fats/carbohydrates 20/30/50%. Sip feeding improves clinical and financial outcomes in inpatient and outpatient practice: shortens the time of staying in the clinic; reduces the number of infectious and non-infectious complications, the rate of repeated hospitalizations; treatment costs; improves the quality of life. OEN is recommended by the European Society for Clinical Nutrition and Metabolism guidelines and by many national guidelines on enteral nutritional support.
... Regarding to cardiovascular disease (CVD), vitamin D deficiency has been linked with the modulation of the immune system, triggering of the pro-inflammatory cell signalling and consequent promotion of the atherogenesis (Nitsa et al. 2018); therefore, the treatment with vitamin D may have a significant role in the prevention of this pathological process (Greco et al. 2018, Ohmura et al. 2018. It has been documented that vitamin D supplementation may protect against endothelial dysfunction, vascular smooth muscle cell proliferation, and migration (Menezes et al. 2014). In addition, vitamin D has been shown to have systemic effects through the changes in adipokines expression. ...
Vitamin D regulates the calcium and phosphorus balance in the body. The activated form of vitamin D (1 α,25-dihydroxyvitamin D) binds to vitamin D receptor which regulates genes that control cell proliferation, differentiation and apoptosis. In the cardiovascular system, the vitamin D receptor is present in cardiomyocytes and the arterial wall. A clear correlation between vitamin D level and cardiovascular diseases is established. Vitamin D deficiency affects the renin-angiotensin system leading to ventricular hypertrophy and eventually to stroke. While clinical trials highlighted the positive effects of vitamin D supplements on cardiovascular disease these still need to be confirmed. This review outlines the association between vitamin D and cardiovascular and renal disease summarising the experimental data of selective cardiovascular disorders.
... Hyperandrogenism may lead to cerebrovascular impairment [27] probably due to the longterm genomic effects of excess androgen [2]. VDD is also linked to cerebrovascular disorders particularly via impaired vessel morphology and reactivity [2,[6][7][8][28][29][30]. In our study, however, neither VDD nor androgen excess alone caused alterations in vessel lumen and wall thickness of female rats, indicating that neither disorder alone causes remodeling in the cerebral arteries of females, at least not within 8 weeks. ...
Hyperandrogenism is a risk factor of cerebrovascular diseases as androgens can alter markedly the regulation of cerebrovascular tone. We examined the combined impact of androgen excess and vitamin D deficiency (VDD), a common co-morbidity in hyperandrogenic disorders, on remodeling and testosterone-induced vascular responses of anterior cerebral arteries (ACA) in order to evaluate the interplay between androgens and VDD in the cerebral vasculature. Male and female Wistar rats were either fed with vitamin D deficient or vitamin D supplemented diet. Half of the female animals from both groups received transdermal testosterone treatment. After 8 weeks, vessel lumen, wall thickness and testosterone-induced vascular tone of isolated ACA were determined using pressure microangiometry and histological examination. Androgen receptor protein expression in the wall of cerebral arteries was examined using immunohistochemistry. In female rats only combined VDD and testosterone treatment decreased the lumen and increased the wall thickness of ACA. In males, however VDD by itself was able to decrease the lumen and increase the wall thickness. Vascular reactivity showed similar alterations: in females, testosterone constricted the ACA only after combined VDD and hyperandrogenism, whereas in males VDD resulted in increased testosterone-induced contractions in spite of decreased androgen receptor expression. In conclusion, a marked interplay between hyperandrogenism and VDD results in inward remodeling and enhanced testosterone-induced constrictions of cerebral arteries, which might compromise the cerebral circulation and thus, increase the risk of stroke in the long term. In addition, the early cerebrovascular manifestation of VDD appears to require androgen excess and thus, depends on gender.
... Calcitriol or 1,25(OH) 2 -D 3 , the active form of vitamin D, has also pleiotropic cardiovascular effects [24,25] in addition to the classic role in phosphate and calcium metabolism. In particular, vitamin D has been reported to exert several favorable effects on the low-grade inflammation associated with atherosclerosis [26][27][28], smooth muscle cell proliferation [29], insulin resistance [30,31], renin-angiotensin-aldosterone system activation [26], dyslipidemia [32], oxidative stress [33], strongly suggesting a potential therapeutic role of vitamin D supplementation. ...
The active form of vitamin D, 1,25-dihydroxycholecalciferol (1,25(OH)2D3), was reported to improve vascular function in patients with diabetes, yet the underlying mechanisms remain to be fully elucidated. Monoamine oxidase (MAO), a mitochondrial enzyme, with two isoforms (A and B) that generates hydrogen peroxide (H2O2) as by-product, has been recently reported to contribute to the pathogenesis of endothelial dysfunction in diabetes. The present study assessed the interaction between vitamin D and MAO in the vascular wall in the setting of type 1 experimental diabetes. To this aim, diabetes was induced in male Wistar rats via a single injection of streptozotocin (STZ, 50 mg/kg, IP) and 1 month later thoracic aortas were harvested and used for organ bath studies and H2O2 measurements. MAO expression was assessed by immunohistochemistry and RT-PCR. Endothelial function was evaluated in isolated aortic rings in the absence vs. presence of 1,25(OH)2D3 (100 nM, 24 h incubation). In diabetic animals, we found a significant reduction in the endothelial-dependent relaxation to acetylcholine and an increased expression of the MAO-A isoform, respectively. Vitamin D significantly improved vascular function, mitigated oxidative stress and decreased MAO-A expression in diabetic vascular preparations. In conclusion, MAO-A is induced in diabetic aortas and vitamin D can improve diabetes-induced endothelial dysfunction by modulating the MAO-A expression.
... Several observational studies have indicated that serum 25-OH vitamin D is inversely associated with BMI, dyslipidemia, inflammatory markers and hypertension in children [11][12][13][14] and adults 14,15 . ...
... Plasma levels of vitamin D have also been found to inversely correlate with RA disease activity [10]. There are indications that vitamin D might have protective effects against atherosclerosis by protecting against VSMC proliferation and migration, endothelial dysfunction, and by modulating inflammatory processes [11]. Even though vitamin D has been linked to inflammation, RA, and coronary artery disease (CAD), the underlying molecular mechanisms are still unclear. ...
Background
Vitamin D has an important role in the immune system, and has been linked to rheumatoid arthritis (RA) and coronary artery disease (CAD). The exact mechanisms by which vitamin D is involved in these processes are still unclear. Therefore, we wanted to search for differences in expression of genes involved in the vitamin D receptor (VDR) activation pathway and genes that are known to alter upon vitamin D stimulation, in the aortic adventitia of CAD patients with and without RA.
Methods
Affymetrix microarray was used to determine gene expression profile in surgical specimens from the adventitia of the ascending aorta of CAD patients with RA (n = 8) and without RA (n = 8) from the Feiring Heart Biopsy Study.
Results
We identified three vitamin D associated genes that were differentially expressed between RA and non-RA patients: Growth arrest and DNA-damage-inducible protein 45 alpha (GADD45A) (FC = 1.47; p = 0.006), Nuclear Receptor Co-repressor 1 (NCOR1) (FC = 1,21; p = 0.005) and paraoxonases 2 (PON2) (FC = -1.37; p = 0.01). High expression of GADD45A in RA tissues was confirmed by real-time qRT-PCR. GADD45A expression correlated with plasma levels of 1,25(OH)2D3 (rs = 0.69; p = 0.003).
Conclusions
Microarray analyses revealed higher expression of GADD45A and NCOR1; and lower expression of PON2 in the aortic adventitia of RA than non-RA patients. Further studies are needed to elucidate if and how GADD45A, NCOR1 and PON2 are involved in the development of accelerated atherosclerosis in RA. In theory, some of these factors might have proatherogenic effects whereas others might reflect an underlying vascular pathology promoting atherogenesis (such as vascular stress).
... Vitamin D improves the bioavailabity of endothelial nitric oxide (NO), the potent vasorelaxing factor and inhibitor of platelet and leucocyte aggregation and adhesion. This occurs via direct enhancement of transcriptional regulator of endothelial nitric oxide synthase (eNOS) (94) and/or exert effect on phosphatidylinositol 3 kinase in endothelial cell (EC), which activates eNOS to catalyse the production of NO from L-arginine (95)(96). By inducing NO production, vitamin D able to stimulate EC proliferation and inhibit apoptosis (97). ...
Diabetes mellitus is an epidemic that is gaining global concern. Chronic hyperglycemia in diabetes induces the excess production of free radicals. The deleterious effects of excess free radicals are encountered by endogenous antioxidant defense system. Imbalance between free radicals production and antioxidants defense mechanisms leads to a condition known as "oxidative stress". Diabetes mellitus is associated with augmented oxidative stress that induced micro- and macrovascular complications, which presents a significant risk for cardiovascular events. Low vitamin D levels in the body have also been reported to be associated with the pathogenesis of diabetes and enhanced oxidative stress. The article is to review available literature and summarize the relationship between oxidative stress and vitamin D levels in diabetes. We also review the effects of vitamin D analogs supplementation in improving oxidative stress in diabetics.
... It is important to consider here that the phenotypic activation of macrophages acquiesce to the availability of 1α,25(OH) 2 D 3 . Vitamin D inhibits T-cell proliferation and decreases expression of pro-inflammatory cytokines which includes inhibition of nuclear factor kappa-B (NF-kB) signaling (Menezes et al., 2014). In addition, 1α,25(OH) 2 D 3 shifts proliferation of T-helper 1 to T-helper 2 phenotypes which dampen the atherogenic response characteristic of T-helper 1 cells. ...
Ectopic or vascular calcification caused primarily by dysregulation of vitamin D and phosphate homeostasis is a major contributor to development of atherosclerosis and cardiovascular disease (CVD). Both deficiencies and excesses of vitamin D affect cardiovascular factors that mediate development of CVD. Atherosclerosis results from accumulation of plaque which is comprised of oxidized lipids, cellular debris, fibrin material and marked calcification. Vitamin D deficiency affects macrophage activation, adhesion and migration, which underlies the “response to injury” hypothesis that initiates atherosclerotic progression. Vitamin D coupled with other epigenetic modifications can subdue cellular inflammation, reduce age-related systolic hypertension and vascular rigidity, and improve overall endothelial functions. Thus, understanding molecular changes and pathways that preserve function and integrity of vascular endothelia and smooth muscle cells will enable investigators to development effective dietary and/or therapeutic measures to remediate CVD. This chapter will explore the major contributions of vitamin D in controlling vascular endothelial and smooth muscle cell integrity, activation and inflammation. Emphasis is placed on: (i) evidence that links vitamin D deficiency to cardiovascular disease, (ii) redox sensitivity and control of the vitamin D receptor (VDR), (iii) role of vitamin D in augmenting the antioxidant network associated with the transcription factor, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and (iv) the association of vitamin D with fibroblast growth factor 23 (FGF23) and Klotho, the endocrine axis which regulates phosphate homeostasis among bone, parathyroid gland, and kidney.
... VDR and CYP27B1 are observed in cardiac myocytes, cardiac fibroblasts, vascular smooth muscle, and endothelial cells, and it appears that activated 1,25(OH) 2 D/VDR pathways may well play some role in cardiovascular function [18]. Experimental studies in laboratory animals have shown that limitation of 1,25(OH) 2 D/VDR signalling can cause increased renin/angiotensin activity with hypertension and cardiac hypertrophy, reduction in the bioavailability of the vasodilator nitric oxide with consequent impaired blood vessel relaxation, endothelial cell dysfunction, upregulation of proinflammatory cytokines, and increased proliferation and migration of vascular smooth muscle cells [4,34,35]. ...
Vitamin D plays an important role in calcium homeostasis and bone metabolism, with the capacity to modulate innate and adaptive immune function, cardiovascular function, and proliferation and differentiation of both normal and malignant keratinocytes. 1,25(OH) 2 D, the biologically active form of vitamin D, exerts most of its functions through the almost universally distributed nuclear vitamin D receptor (VDR). Upon stimulation by 1,25(OH) 2 D, VDR forms a heterodimer with the retinoid X receptor (RXR). In turn, VDR/RXR binds to DNA sequences termed vitamin D response elements in target genes, regulating gene transcription. In order to exert its biological effects, VDR signalling interacts with other intracellular signalling pathways. In some cases 1,25(OH) 2 D exerts its biological effects without regulating either gene expression or protein synthesis. Although the regulatory role of vitamin D in many biological processes is well documented, there is not enough evidence to support the therapeutic use of vitamin D supplementation in the prevention or treatment of infectious, immunoinflammatory, or hyperproliferative disorders. In this review we highlight the effects of 1,25(OH) 2 D on bone and calcium homeostasis, on cancer, and refer to its effects on the cardiovascular and immune systems.
... Multiple forms of vitamin D are present within the body in varying concentrations ( Fig. 15.1). Regardless of where this vitamin is derived, all forms must be converted to 25 hydroxy-vitamin D (25OHD) and then activated to 1,25(OH) 2 D. [1] When the skin is exposed to UV light, the naturally occurring 7-dehydrocholesterol is converted to Vitamin D 3 (cholecalciferol, D3). D3 may also be ingested from animal sources. ...
Vitamin D levels and metabolism may play a role in the pathogenesis and treatment of atherosclerosis and subsequent cardiovascular health. Herein, we discuss both normal and disordered vitamin D metabolism as it pertains to atherosclerosis, and we review major clinical trials regarding vitamin D levels and effects of supplementation. Although there are no official recommendations for vitamin D as it applies to atherosclerosis, it is clear that these two entities are linked. Further study of the complex association between vitamin D and atherosclerosis, as well as the effects of supplementation, are recommended.
... Atherosclerosis, as a hallmark of cardiovascular disorders, is a complex process that can progress for decades before presentation. 2 Inflammatory changes, osteogenesis and bone-forming mechanisms, angiogenesis, and endothelial dysfunction are examples of important issues associated with the pathogenesis of atherosclerosis, which are directly or indirectly affected by vitamin D. [3][4][5][6][7][8] Several studies have been performed on the association between vitamin D status and different aspects of cardiovascular disorders, including metabolic syndrome, 9 hypertension, 10,11 calcified atherosclerotic plaques, 12,13 severity of luminal stenosis in coronary arteries, 14,15 tortuosity of coronary arteries, 16 and even the final outcomes or lethal events of coronary artery disease (CAD). 17 In this regard, the need for increased attention has been proposed, suggesting the role of vitamin D deficiency as a risk factor for CAD. ...
Background
Vitamin D deficiency, as a predisposing factor for coronary artery disease (CAD), is a subject of increasing interest. However, its role as a risk factor has not been proven. This study aimed to investigate the relationship between serum vitamin D levels and CAD.
Materials and methods
Using a cross-sectional design, 180 patients who were candidates for coronary computed tomography angiography (CCTA) were selected. Serum levels of vitamin D were measured and compared with the results of CCTA (including calcium score, and presence and severity of coronary artery involvement due to atherosclerotic plaques).
Results
The mean age of the participants was 60.5±10.6 years and the mean serum vitamin D level was 26.2±15.9 ng/dL (range, 3.5–83.2 ng/dL). Overall, 6.1% of the participants (n=11) had vitamin D deficiency, 56.1% (n=101) had insufficient levels of vitamin D, and 37.8% (n=68) had sufficient levels of vitamin D. The mean serum vitamin D level was significantly lower in patients with severe CAD (P=0.004). The serum vitamin D level in the “positive for CAD” group was 20.98 ng/mL, significantly lower than the level in the “negative for CAD” group (30.47 ng/mL; P<0.001). The mean calcium score among participants was 533.5±87.9. Based on the Spearman test, a significant negative correlation (−0.21) was detected between the serum vitamin D level and coronary artery calcium score (CACS) (P=0.005). Conversely, the mean CACS in the vitamin D deficient group was significantly higher than in the insufficient and sufficient vitamin D groups (P<0.001 for both comparisons).
Conclusion
Vitamin D deficiency was associated with coronary artery calcification and severity of coronary artery stenosis in Iranian patients.
... Vitamin D has been shown to protect against endothelial dysfunction, vascular smooth muscle cell proliferation and migration, and modulation of the immune system. In addition, vitamin D also may have antiinflammatory effect and systemic effects on insulin resistance [14]. ...
Objectives: Vitamin D deficiency has been shown to influence the development of some cardiovascular disease. In this study, the association between the existence of coronary artery plaque and vitamin D was examined among participants who were not previously diagnosed with coronary artery disease.
Methods: A total of 339 participants (246 men and 93 women) who visited a health examination center for check-up including blood test for serum vitamin D level and coronary computed tomography angiography (CCTA) were selected for this study.
Results: Among the total 339 participants, 106 displayed coronary artery plaques. The serum 25-hydroxy vitamin D (25(OH)D) level of the group with plaque was lower than that of the group without (17.7 ± 7.72 ng/mL vs. 19.6 ± 7.12 ng/mL, P = 0.0316). The group with plaque had higher incidence rates of diabetes mellitus, hypertension, and dyslipidemia than that without (P = 0.0078, P = 0.0065, and P = 0.0174, respectively). The former displayed higher serum glucose and glycated hemoglobin levels than the latter (P = 0.0055 and P = 0.0137, respectively). The group with plaque showed higher systolic and diastolic blood pressure than that without (P
... Inadequate vitamin D status is common in many parts of the world [12] and is associated with obesity and related chronic disease [13][14][15][16]. The main source of vitamin D is through endogenous production, whereby solar UV-B irradiates 7-dehydrocholesterol present in the skin to generate cholecalciferol [17,18], which is subsequently activated in the liver and kidney. ...
Causal links between vitamin D status [25(OH)D] and systemic inflammation were examined through a systematic review of randomized controlled trials (RCTs). Selected RCTs were ⩾12 weeks, conducted in adults free of acute inflammatory disease, and of high-quality (Jadad score ⩾3). Of 14 studies that met our criteria, 9 studies (15 study arms) permitted extraction of data. There was no effect on the weighted mean difference (WMD) of IL-6 (WMD (95% confidence interval)=0.1, (-0.166, 0.366) pg/ml, P=0.462) or C-reactive protein (CRP) (WMD=-0.324, (-1.007, 0.359) mg/l, P=0.352). Subgroup analyses of trials achieving ⩾80 nmol/l indicated a trend for lower CRP (WMD=-0.834, (-1.726, 0.058) mg/l, P=0.067), however heterogeneity was significant (I(2)=66.7%, P=0.017). Studies employing a low dose (<1000 IU/d) showed increased CRP (WMD=0.615, (0.132, 1.098), P=0.013). In contrast, ⩾1000 IU/d had a favourable effect on CRP (WMD=-0.939, (-1.805, -0.073), P=0.034) but heterogeneity was significant (I(2)=61.3%, P=0.017). Meta-regression indicated that older age predicted a significant decrease in IL-6 (β=-0.02, (-0.034, -0.006) pg/ml, P=0.013) and CRP (β=-0.06, (-0.103, -0.017), P=0.01), whereas a greater percentage of females (β=0.027, (0.011, 0.044), P=0.004) and longer study duration independently predicted a higher WMD for CRP (β=0.049, (0.018, 0.079), P=0.005). Available high-quality RCTs did not support a beneficial effect of cholecalciferol on systemic IL-6 and CRP. Future studies should consider the confounding effects of age, gender and study duration, while possibly targeting an achieved 25(OH)D ⩾80 nmol/l.European Journal of Clinical Nutrition advance online publication, 10 May 2017; doi:10.1038/ejcn.2017.67.
... Several observational studies have indicated that serum 25-OH vitamin D is inversely associated with BMI, dyslipidemia, inflammatory markers and hypertension in children [11][12][13][14] and adults 14,15 . ...
Background
Vitamin D deficiency is a prevalent and important global health problem. Because of its role in growth and development, vitamin D status is likely to be particularly important in adolescent girls. Here, we explored the effects of high-dose vitamin D supplementation on cardio-metabolic risk factors.
Methods
We have examined the effects of vitamin D supplementation on cardio-metabolic risk factors in 988 healthy adolescent girls in Iran. Fasting blood samples and anthropometric measurements were obtained at baseline and after supplementation with high-dose vitamin D. All individuals took a capsule of 50,000 IU vitamin D/week for nine weeks. The study was completed by 940 participants.
Results
The prevalence of vitamin D deficiency was 90% at baseline, reducing to 16.3% after vitamin D supplementation. Vitamin supplementation was associated with a significant increase in serum concentrations of 25 (OH) vitamin D and calcium. There were significant reductions in diastolic blood pressure, heart rate, waist circumference and serum fasting blood glucose, total- and low-density lipoprotein-cholesterol after the nine-week period on vitamin D treatment, but no significant effects were observed on body mass index, systolic blood pressure or serum high-density lipoprotein cholesterol and triglyceride.
Conclusion
Vitamin D supplementation had beneficial effects on cardio-metabolic profile in adolescent girls.
Introduction and Aim: Cardiovascular diseases are the leading cause of death worldwide. The prevalence of cardiovascular disease in India is continuously on the rise owing to the socioeconomic changes the country is undergoing. In order to minimise the mortality due to cardiovascular disease, early detection and control of modifiable risk factors is of utmost importance. We evaluated the correlation of vitamin D deficiency, one such possible modifiable risk factor, and the severity of CAD in patients at a hospital in Southern Karnataka. Unfortunately, relevant data regarding vitamin D deficiency in coronary artery disease pertaining to the Indian subcontinent is scarce. Thus, the results of our study can provide further evidence for the potential therapeutic benefit of Vitamin D in patients with cardiovascular risk factors, which in the long run can significantly reduce the morbidity and mortality of CAD. Materials and Methods: A case-control study with 142 subjects was conducted in Kasturba Hospital. Based on coronary angiogram findings, cases were categorised as having single, double, triple or multi vessel disease. Vitamin D level was quantified into 3 categories: normal (>30ng/ml), insufficient (20-30ng/ml) and deficient (<20ng/ml). Results: Vitamin D deficiency was statistically significantly and inversely related to the number of vessels involved (multi vessel disease-83.3%, triple vessel disease-80%, double vessel disease-28.6% and single vessel disease-21.7%). The relationship between vitamin D levels and syntax scoring showed a negative correlation (-0.339). Multiple linear regression analysis showed that the severity of CAD was correlated to diabetes and vitamin D deficiency with p-value of 0.014. Conclusion: Both our results and those of previous studies suggest that vitamin D could have a potential therapeutic effect in CAD.
Background. Obesity and vitamin D deficiency in children are widespread in economically developed countries. Among children with obesity and components of the metabolic syndrome, vitamin D deficiency is more common than in children with a normal body mass index (BMI). The growth of metabolic disorders, atherosclerosis, early onset of type 2 diabetes mellitus lead to fatal vascular accidents in young people, and therefore the search for new ways of early diagnosis of these processes is relevant. Aim. To study of the relationship of endothelial dysfunction with vitamin D deficiency, obesity and associated metabolic disorders among adolescents in Saint Petersburg. Materials and methods. 5 adolescents aged 1416 years (150.76 years) with primary obesity were examined. Anthropometric parameters were studied: waist circumference, weight, height, calculation of BMI, stage of puberty according to Tanner. Laboratory examination included the following parameters: serum glucose, cholesterol, triglycerides, high density lipoproteins, low density lipoproteins, insulin, 25(OH)D. Atherogenicity index (AI), insulin resistance index (HOMA-IR), vitamin D sufficiency were calculated. Endothelial function was assessed by the value of the reactive hyperemia index (RHI), automatically calculated by the EndoPAT 2000 device (Itamar Medical, Israel). Results. All examined patients had abdominal obesity (median BMI 33.5 kg/m2 [30.9; 34.2]) and reduced vitamin D supply (median 25(OH)D 17.2 ng/ml). Hypercholesterolemia and dyslipidemia due to an increase in low density lipoproteins were diagnosed in 1 (20%) case. Dyslipidemia due to a decrease in high density lipoproteins was detected in 3 (60%) patients. An increase in IA was found in 4 (80%) people. Insulin resistance was present in 60% of the examined, the median value of HOMA-IR was 5.6. The median RHI was 1.74 [1.72; 2.13]. Optimum RHI values were observed in 2 (40%) patients; in most (60%) adolescents, the RHI values corresponded to subnormal values and were close to the lower limit of this zone. A significant inverse correlation of RHI with AI was obtained (R=-0.63, p0.05). Conclusion. Taking into account the risk factors previously identified in the examined patients (dyslipidemia, insulin resistance, reduced vitamin D supply), endothelial dysfunction in these patients was regarded as a cardiovascular risk factor. A manageable risk factor is a reduced supply of vitamin D, which can be corrected by an additional donation of cholecalciferol.
Mechanistic understanding of atherosclerosis is largely hampered by the lack of a suitable in vitro human arterial model that recapitulates the arterial wall structure, and the interplay between different cell types and the surrounding extracellular matrix (ECM). This work introduces a novel microfluidic endothelial cell (EC)-smooth muscle cell (SMC) 3D co-culture platform that replicates the structural and biological aspects of the human arterial wall for modeling early atherosclerosis. Using a modified surface tension-based ECM patterning method, we established a well-defined intima-media-like structure, and identified an ECM composition (collagen I and Matrigel mixture) that retains the SMCs in a quiescent and aligned state, characteristic of a healthy artery. Endothelial stimulation with cytokines (IL-1β and TNFα) and oxidized low-density lipoprotein (oxLDL) was performed on-chip to study various early atherogenic events including endothelial inflammation (ICAM-1 expression), EC/SMC oxLDL uptake, SMC migration, and monocyte-EC adhesion. As a proof-of-concept for drug screening applications, we demonstrated the atheroprotective effects of vitamin D (1,25(OH)2D3) and metformin in mitigating cytokine-induced monocyte-EC adhesion and SMC migration. Overall, the developed arterial wall model facilitates quantitative and multi-factorial studies of EC and SMC phenotype in an atherogenic environment, and can be readily used as a platform technology to reconstitute multi-layered ECM tissue biointerfaces.
Cognitive dysfunction is a common feature in systemic lupus erythematosus (SLE) patients, with a prevalence of ranging from 55–80% in SLE patients (Ainiala et al., Arthritis Rheum 45:419–423, 2001; Brey et al., Neurology 58:1214–1220, 2002; Hanly et al., J Rheumatol 31:2156–2162, 2004; Sanna et al., J Rheumatol 30:985–992, 2003; Sibbitt et al., J Rheumatol 29:1536–1542, 2002). Cognitive impairment often involves the subcortical brain, causing difficulties with working memory as well as a reduction in information-processing and executive functioning, such as planning, organizing, or multi-tasking (Leritz et al., J Int Neuropsychol Soc 6:821–825, 2000). The etiology of cognitive dysfunction in SLE is still under investigation, with current studies demonstrating that cognitive dysfunction cannot be fully explained by SLE disease activity or treatments or prior strokes (Brey et al., Neurology 58:1214–1220, 2002; Rivest et al., J Rheumatol 27:680–684, 2000). Alternative explanations, such as infection, malignancy, medication adverse effect (e.g. steroid-induced psychosis), metabolic disturbances (e.g. uremia) need to be aggressively evaluated and excluded (“The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes,” Arthritis Rheum, 42:599–608, 1999; Futrell et al., Neurology 42:1649–1657, 1992; West et al., Am J Med 99:153–163, 1995).
Objectives:
To investigate the differences in characteristics of carotid plaques between patients Xining at high altitude and Jinan at sea level using magnetic resonance (MR) imaging.
Methods:
Subjects were recruited from a cross-sectional, observational, multicenter imaging study of CARE-II study. Forty-nine (mean age 63.3 ± 12.0 years, 33 males) and 51 (mean age 64.5 ± 12.0 years, 34 males) patients were recruited from a site located in a high altitude region and a site located near sea level, respectively. All patients underwent multicontrast MR vessel wall imaging for carotid arteries on 3.0 T MR scanner. The carotid plaques features were compared between 2 patient groups.
Results:
Compared with patients at sea level, those at high altitude had significantly greater lumen area (58.5 ± 17.8 mm2 versus 50.0 ± 19.6 mm2, P = .008), smaller maximum normalized wall index (48.6% ± 14.2% versus 57.8% ± 16.3%, P = .002), and smaller percentage volume of calcium (0.9% versus 5.6%, P < .001) in the symptomatic carotid artery. After adjustment for clinical risk factors including age, sex, systolic blood pressure, LDL-C, and statin use, these differences in plaque morphology and composition remained statistically significant. After further adjustment for normalized wall index as a measure of plaque burden, percentage volume of calcification was still significantly smaller in patients at high altitude area than that in patients at sea level area (P = .047).
Conclusion:
Symptomatic subjects from a high altitude area have lower plaque burden and less calcification in the carotid artery compared to those from an area near sea level.
Heart failure (HF) with reduced ejection fraction (HFrEF) presents as the severest phenotype on the spectrum of HF. Although great progress has been made with respect to its treatment over the past 3 decades, morbidity and mortality remain high, posing a big burden on human health. Recent evidence suggests vitamin D has a critical role in maintaining heart health through activation of the vitamin D receptor expressed in cardiomyocytes, and vitamin D deficiency may be implicated in the pathophysiology of HFrEF through activation of the renin-angiotensin system, impaired calcium handling, exaggerated inflammation, secondary hyperparathyroidism, pro-fibrotic properties, and proatherogenic potential. Additionally, epidemiological data disclosed that vitamin D deficiency is highly prevalent in patients with HFrEF and is associated with poor clinical outcomes. However, randomized control trials of vitamin D supplementation in HF, especially in HFrEF, have shown inconsistent results. Thus, this article aims to review the epidemiology, pathophysiology, and prognostic value of vitamin D deficiency in HF, with a special focus on randomized control trials associated with vitamin D supplementation in patients with HFrEF.
Since the successful conquest of many acute, communicable (infectious) diseases through the use of vaccines and antibiotics, the currently most prevalent diseases are chronic and progressive in nature, and are all accompanied by inflammation. These diseases include neurodegenerative (e.g. Alzheimer's, Parkinson's), vascular (e.g. atherosclerosis, pre‐eclampsia, type 2 diabetes) and autoimmune (e.g. rheumatoid arthritis and multiple sclerosis) diseases that may appear to have little in common. In fact they all share significant features, in particular chronic inflammation and its attendant inflammatory cytokines. Such effects do not happen without underlying and initially ‘external’ causes, and it is of interest to seek these causes. Taking a systems approach, we argue that these causes include (i) stress‐induced iron dysregulation, and (ii) its ability to awaken dormant, non‐replicating microbes with which the host has become infected. Other external causes may be dietary. Such microbes are capable of shedding small, but functionally significant amounts of highly inflammagenic molecules such as lipopolysaccharide and lipoteichoic acid. Sequelae include significant coagulopathies, not least the recently discovered amyloidogenic clotting of blood, leading to cell death and the release of further inflammagens. The extensive evidence discussed here implies, as was found with ulcers, that almost all chronic, infectious diseases do in fact harbour a microbial component. What differs is simply the microbes and the anatomical location from and at which they exert damage. This analysis offers novel avenues for diagnosis and treatment.
Background and purpose
Vitamin D deficiency (VDD) is a global health problem, which can lead to several pathophysiological consequences including cardiovascular diseases. Its impact on the cerebrovascular system is not well understood. The goal of the present work was to examine the effects of VDD on the morphological, biomechanical and functional properties of cerebral arterioles.
Methods
Four-week-old male Wistar rats (n = 11 per group) were either fed with vitamin D deficient diet or received conventional rat chow with per os vitamin D supplementation. Cardiovascular parameters and hormone levels (testosterone, androstenedione, progesterone and 25-hydroxyvitamin D) were measured during the study. After 8 weeks of treatment anterior cerebral artery segments were prepared and their morphological, biomechanical and functional properties were examined using pressure microangiometry. Resorcin-fuchsin and smooth muscle actin staining were used to detect elastic fiber density and smooth muscle cell counts in the vessel wall, respectively. Sections were immunostained for eNOS and COX-2 as well.
Results
VDD markedly increased the wall thickness, the wall-to-lumen ratio and the wall cross-sectional area of arterioles as well as the number of smooth muscle cells in the tunica media. As a consequence, tangential wall stress was significantly lower in the VDD group. In addition, VDD increased the myogenic as well as the uridine 5’-triphosphate-induced tone and impaired bradykinin-induced relaxation. Decreased eNOS and increased COX-2 expression were also observed in the endothelium of VDD animals.
Conclusions
VDD causes inward hypertrophic remodeling due to vascular smooth muscle cell proliferation and enhances the vessel tone probably because of increased vasoconstrictor prostanoid levels in young adult rats. In addition, the decreased eNOS expression results in endothelial dysfunction. These morphological and functional alterations can potentially compromise the cerebral circulation and lead to cerebrovascular disorders in VDD.
The renin-angiotensin system (RAS) is a central regulator of renal and cardiovascular functions. Excess activation of the RAS leads to renal and cardiovascular disorders, such as hypertension and chronic kidney disease, and is the major risk factor for stroke, myocardial infarction, congestive heart failure, atherosclerosis, and renal failure. In addition, the RAS is also involved in the pathology of other tissues. Mounting epidemiological and clinical evidence has demonstrated an association of vitamin D deficiency or insufficiency with increased risks of renal and cardiovascular diseases, but the molecular basis remains poorly defined. The discovery of the vitamin D hormone as an endocrine repressor of the RAS provides a potential explanation for this association. 1,25 dihydroxyvitamin D3 downregulates the expression of renin, the rate-limiting enzyme of the renin-angiotensin cascade. Vitamin D deficiency leads to overexpression of renin and thus activation of the RAS, causing renal and cardiovascular injuries. Defects in the vitamin D receptor signaling also promote local RAS activation in other tissues leading to detrimental effects. Physiologically the vitamin D hormone may play a role in maintaining the homeostasis of the renal and cardiovascular systems via suppressing the RAS. Pharmacologically, vitamin D analogs may be used to target the RAS for disease management.
Atherosclerosis is a progressive and multifactorial disease which occurs under the influence of various risk factors including endothelial dysfunction (ED), oxidative stress, and low-density lipoprotein (LDL) oxidation. In contract to the initial hypotheses on the usefulness of vitamin E supplementation for cardiovascular disease prevention, large outcome trials showed consumption of vitamin E has no obvious effect on cardiovascular disease and, in some cases, it may even increase the rate of mortality. This seemingly unexpected finding may be due to the opposite effects of vitamin E compounds. Vitamin E is a group of compounds which have different and even opposing effects, yet in most of the studies, the exact consumed component of vitamin E is not determined. It appears that the combined consumption of gamma-tocopherol, vitamin C, D, and tetrahydrobiopterin (BH4) may be extremely effective in both preventing atherogenesis and suppressing plaque development. In this regard, one of main issues is effect of vitamins E and D deficiency on microRNAs network in atherosclerosis. Various studies have indicated that miRNAs have key roles in atherosclerosis pathogenesis. The deficiency of vitamins E and D could provide a deregulation for miRNAs network and these events could lead to progression of atherosclerosis. Here, we highlighted a variety of mechanisms involve in the progression of atherosclerosis and effects of vitamins D and E on these mechanisms. Moreover, we summarized miRNAs involve in atherosclerosis and their regulation by vitamins E and D deficiency.
Vitamin D has received a lot of attention recently as a result of a meteoric rise in the number of publications showing that vitamin D plays a crucial role in a plethora of physiological functions and associating vitamin D deficiency with many acute and chronic illnesses including disorders of calcium metabolism, autoimmune diseases, some cancers, type 2 diabetes mellitus, infectious diseases and cardiovascular disease. The recent data on vitamin D from experimental, ecological, case-control, retrospective and prospective observational studies, as well as smaller intervention studies, are significant and confirm the sunshine vitamin's essential role in a variety of physiological and preventative functions. The results of these studies justify the recommendation to improve the general vitamin D status in children and adults by means of a healthy approach to sunlight exposure, consumption of foods containing vitamin D and supplementation with vitamin D preparations. In general, closer attention should therefore be paid to vitamin D deficiency in medical and pharmaceutical practice than has been the case hitherto.
Vitamin D is the sunshine vitamin that has been produced on this earth for more than 500 million years. During exposure to sunlight 7-dehydrocholesterol in the skin absorbs UV B radiation and is converted to previtamin D3 which in turn isomerizes into vitamin D3. Previtamin D3 and vitamin D3 also absorb UV B radiation and are converted into a variety of photoproducts some of which have unique biologic properties. Sun induced vitamin D synthesis is greatly influenced by season, time of day, latitude, altitude, air pollution, skin pigmentation, sunscreen use, passing through glass and plastic, and aging. Vitamin D is metabolized sequentially in the liver and kidneys into 25-hydroxyvitamin D which is a major circulating form and 1,25-dihydroxyvitamin D which is the biologically active form respectively. 1,25-dihydroxyvitamin D plays an important role in regulating calcium and phosphate metabolism for maintenance of metabolic functions and for skeletal health. Most cells and organs in the body have a vitamin D receptor and many cells and organs are able to produce 1,25-dihydroxyvitamin D. As a result 1,25-dihydroxyvitamin D influences a large number of biologic pathways which may help explain association studies relating vitamin D deficiency and living at higher latitudes with increased risk for many chronic diseases including autoimmune diseases, some cancers, cardiovascular disease, infectious disease, schizophrenia and type 2 diabetes. A three-part strategy of increasing food fortification programs with vitamin D, sensible sun exposure recommendations and encouraging ingestion of a vitamin D supplement when needed should be implemented to prevent global vitamin D deficiency and its negative health consequences.
The plethora of vitamin D studies over the recent years highlight the pleomorphic effects of vitamin D outside its conventional role in calcium and bone homeostasis. Vitamin D deficiency, though common and known, still faces several challenges among the medical community in terms of proper diagnosis and correction. In this review, the different levels of vitamin D and its clinical implications are highlighted. Recommendations and consensuses for the appropriate dose and duration for each vitamin D status are also emphasized.
1alpha ,25-Dihydroxyvitamin D3 [1,25-(OH)2D3], the biologically active metabolite of vitamin D3, inhibited synthesis of gamma -interferon (IFN-gamma ) by phytohemagglutininactivated peripheral blood lymphocytes (PBLs). A significant reduction of IFN-gamma protein levels in PBL culture medium was achieved with a physiologic 1,25-(OH)2D3 concentration (0.1 nM). 1,25-(OH)2D3 also inhibited accumulation of IFN-gamma mRNA in activated PBLs in a dose-dependent fashion. The ability of 1,25-(OH)2D3 to modulate IFN-gamma protein synthesis was unaltered in the presence of high concentrations of recombinant human interleukin 2. The suppression of IFN-gamma synthesis by PBLs was specific for 1,25-(OH)2D3; the potencies of other vitamin D3 metabolites were correlated with their affinities for the cellular 1,25-(OH)2D3 receptor. The time course of 1,25-(OH)2D3 receptor expression in phytohemagglutinin-activated PBLs was correlated with the time course of 1,25-(OH)2D3-mediated inhibition of IFN-gamma synthesis. In selected experiments, T-lymphocyte-enriched cell preparations were utilized. In these experiments, 1,25-(OH)2D3 was equally active as in PBL preparations. Finally, we examined the effects of 1,25-(OH)2D3 on the constitutive IFN-gamma production by two human T-lymphocyte lines transformed by human T-lymphotropic virus type I. The cell lines were established from a normal donor (cell line S-LB1) and from a patient with vitamin D-dependent rickets type 2 (cell line Ab-VDR). IFN-gamma synthesis by S-LB1 cells was inhibited in a dose-dependent fashion by 1,25-(OH)2D3, whereas IFN-gamma synthesis by Ab-VDR cells was not altered by 1,25-(OH)2D3. The data presented in this study provide further evidence for a role of 1,25-(OH)2D3 in immunoregulation.
Vitamin D is well known for its role in calcium regulation and bone health, but emerging literature tells of vitamin D's central role in other vital body processes, such as: signaling gene response, protein synthesis, hormone synthesis, immune response, plus, cell turnover and regeneration. The discovery of the vitamin D receptor within the muscle suggested a significant role for vitamin D in muscle tissue function. This discovery led researchers to question the impact that vitamin D deficiency could have on athletic performance and injury. With over 77% of the general population considered vitamin D insufficient, it's likely that many athletes fall into the same category. Research has suggested vitamin D to have a significant effect on muscle weakness, pain, balance, and fractures in the aging population; still, the athletic population is yet to be fully examined. There are few studies to date that have examined the relationship between vitamin D status and performance, therefore, this review will focus on the bodily roles of vitamin D, recommended 25(OH)D levels, vitamin D intake guidelines and risk factors for vitamin D insufficiency in athletes. In addition, the preliminary findings regarding vitamin D's impact on athletic performance will be examined.
Vitamin D is characterized as a regulator of homeostasis of bone and mineral metabolism, but it can also provide nonskeletal actions because vitamin D receptors have been found in various tissues including the brain, prostate, breast, colon, pancreas, and immune cells. Bone metabolism, modulation of the immune response, and regulation of cell proliferation and differentiation are all biological functions of vitamin D. Vitamin D may play an important role in modifying the risk of cardiometabolic outcomes, including diabetes mellitus (DM), hypertension, and cardiovascular disease. The incidence of type 2 DM is increasing worldwide and results from a lack of insulin or inadequate insulin secretion following increases in insulin resistance. Therefore, it has been proposed that vitamin D deficiency plays an important role in insulin resistance resulting in diabetes. The potential role of vitamin D deficiency in insulin resistance has been proposed to be associated with inherited gene polymorphisms including vitamin D-binding protein, vitamin D receptor, and vitamin D 1alpha-hydroxylase gene. Other roles have been proposed to involve immunoregulatory function by activating innate and adaptive immunity and cytokine release, activating inflammation by upregulation of nuclear factor κB and inducing tumor necrosis factor α, and other molecular actions to maintain glucose homeostasis and mediate insulin sensitivity by a low calcium status, obesity, or by elevating serum levels of parathyroid hormone. These effects of vitamin D deficiency, either acting in concert or alone, all serve to increase insulin resistance. Although there is evidence to support a relationship between vitamin D status and insulin resistance, the underlying mechanism requires further exploration. The purpose of this paper was to review the current information available concerning the role of vitamin D in insulin resistance.
Significant controversy has emerged over the last decade concerning the effects of vitamin D on skeletal and nonskeletal tissues. The demonstration that the vitamin D receptor is expressed in virtually all cells of the body and the growing body of observational data supporting a relationship of serum 25-hydroxyvitamin D to chronic metabolic, cardiovascular, and neoplastic diseases have led to widespread utilization of vitamin D supplementation for the prevention and treatment of numerous disorders. In this paper, we review both the basic and clinical aspects of vitamin D in relation to nonskeletal organ systems. We begin by focusing on the molecular aspects of vitamin D, primarily by examining the structure and function of the vitamin D receptor. This is followed by a systematic review according to tissue type of the inherent biological plausibility, the strength of the observational data, and the levels of evidence that support or refute an association between vitamin D levels or supplementation and maternal/child health as well as various disease states. Although observational studies support a strong case for an association between vitamin D and musculoskeletal, cardiovascular, neoplastic, and metabolic disorders, there remains a paucity of large-scale and long-term randomized clinical trials. Thus, at this time, more studies are needed to definitively conclude that vitamin D can offer preventive and therapeutic benefits across a wide range of physiological states and chronic nonskeletal disorders.
To examine the prospective associations of baseline vitamin D [25-hydroxyvitamin D; 25(OH)D] with insulin resistance (IR), β-cell function, and glucose homeostasis in subjects at risk for type 2 diabetes.
We followed 489 subjects, aged 50 ± 10 years, for 3 years. At baseline and follow-up, 75-g oral glucose tolerance tests (OGTTs) were administered. IR was measured using the Matsuda index (IS(OGTT)) and the homeostasis model assessment of IR (HOMA-IR), β-cell function was determined using both the insulinogenic index divided by HOMA-IR (IGI/IR) and the insulin secretion sensitivity index-2 (ISSI-2), and glycemia was assessed using the area under the glucose curve (AUC(glucose)). Regression models were adjusted for age, sex, ethnicity, season, and baseline value of the outcome variable, as well as baseline and change in physical activity, vitamin D supplement use, and BMI.
Multivariate linear regression analyses indicated no significant association of baseline 25(OH)D with follow-up IS(OGTT) or HOMA-IR. There were, however, significant positive associations of baseline 25(OH)D with follow-up IGI/IR (β = 0.005, P = 0.015) and ISSI-2 (β = 0.002, P = 0.023) and a significant inverse association of baseline 25(OH)D with follow-up AUC(glucose) (β = -0.001, P = 0.007). Progression to dysglycemia (impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes) occurred in 116 subjects. Logistic regression analyses indicated a significant reduced risk of progression with higher baseline 25(OH)D (adjusted odds ratio 0.69 [95% CI 0.53-0.89]), but this association was not significant after additional adjustment for baseline and change in BMI (0.78 [0.59-1.02]).
Higher baseline 25(OH)D independently predicted better β-cell function and lower AUC(glucose) at follow-up, supporting a potential role for vitamin D in type 2 diabetes etiology.
In response to a thermal stress, skin blood flow (BF) increases to protect the skin from damage. When a very warm, noxious, heat source (44 °C) is applied to the skin, the BF increases disproportionately faster than the heat stress that was applied, creating a safety mechanism for protecting the skin. In the present investigation, the rate of rise of BF in response to applied heat at temperatures between 32 °C and 40 °C was examined as well as the thermal transfer to and from the skin with and without BF in younger and older subjects to see how the skin responds to a non-noxious heat source. Twenty male and female subjects (10 - 20-35 years, 10 - 40-70 years) were examined. The arms of the subjects were passively heated for 6 min with and without vascular occlusion by a thermode at temperatures of 32, 36, 38 or 40 °C. When occlusion was not used during the 6 min exposure to heat, there was an exponential rise in skin temperature and BF in both groups of subjects over the 6-min period. However, the older subjects achieved similar skin temperatures but with the expenditure of fewer calories from the thermode than was seen for the younger subjects (p<0.05). BF was significantly less in the older group than the younger group at rest and after exposure to each of the three warmest thermode temperatures (p<0.05). As was seen for noxious temperatures, after a delay, the rate of rise of BF at the three warmest thermode temperatures was faster than the rise in skin temperature in the younger group but less in the older group of subjects. Thus, a consequence of ageing is reduced excess BF in response to thermal stress increasing susceptibility to thermal damage. This must be considered in modelling of BF.
Calcitriol, the hormonally active form of vitamin D, exerts multiple anti-proliferative and pro-differentiating actions including cell cycle arrest and induction of apoptosis in many malignant cells, and the hormone is currently being evaluated in clinical trials as an anti-cancer agent. Recent research reveals that calcitriol also exhibits multiple anti-inflammatory effects. First, calcitriol inhibits the synthesis and biological actions of pro-inflammatory prostaglandins (PGs) by three mechanisms: i) suppression of the expression of cyclooxygenase-2, the enzyme that synthesizes PGs; ii) up-regulation of the expression of 15-hydroxyprostaglandin dehydrogenase, the enzyme that inactivates PGs; and iii) down-regulation of the expression of PG receptors that are essential for PG signaling. The combination of calcitriol and nonsteroidal anti-inflammatory drugs results in a synergistic inhibition of the growth of prostate cancer (PCa) cells and offers a potential therapeutic strategy for PCa. Second, calcitriol increases the expression of mitogen-activated protein kinase phosphatase 5 in prostate cells resulting in the subsequent inhibition of p38 stress kinase signaling and the attenuation of the production of pro-inflammatory cytokines. Third, calcitriol also exerts anti-inflammatory activity in PCa through the inhibition of nuclear factor-kappaB signaling that results in potent anti-inflammatory and anti-angiogenic effects. Other important direct effects of calcitriol as well as the consequences of its anti-inflammatory effects include the inhibition of tumor angiogenesis, invasion, and metastasis. We hypothesize that these anti-inflammatory actions, in addition to the other known anti-cancer effects of calcitriol, play an important role in its potential use as a therapeutic agent for PCa. Calcitriol or its analogs may have utility as chemopreventive agents and should be evaluated in clinical trials in PCa patients with early or precancerous disease.
Vitamin D deficiency is a highly prevalent condition, present in approximately 30% to 50% of the general population. A growing body of data suggests that low 25-hydroxyvitamin D levels may adversely affect cardiovascular health. Vitamin D deficiency activates the renin-angiotensin-aldosterone system and can predispose to hypertension and left ventricular hypertrophy. Additionally, vitamin D deficiency causes an increase in parathyroid hormone, which increases insulin resistance and is associated with diabetes, hypertension, inflammation, and increased cardiovascular risk. Epidemiologic studies have associated low 25-hydroxyvitamin D levels with coronary risk factors and adverse cardiovascular outcomes. Vitamin D supplementation is simple, safe, and inexpensive. Large randomized controlled trials are needed to firmly establish the relevance of vitamin D status to cardiovascular health. In the meanwhile, monitoring serum 25-hydroxyvitamin D levels and correction of vitamin D deficiency is indicated for optimization of musculoskeletal and general health.
There is now solid evidence that T cell adaptive immunity is involved in atherogenesis. While initial studies have focused on the pathogenic arm of the immune response, more recent work clearly suggests an important role for several subsets of regulatory T cells in the protection against lesion development. Here, we review the current knowledge on the role of both pathogenic and regulatory adaptive T cell immunity in atherosclerosis, generated mainly from the study of mouse models of the disease.
Tropoelastin expression is down-regulated by exposure to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), and we present data indicating that this repression is primarily controlled by a posttranscriptional mechanism. Steady-state and functional levels of tropoelastin mRNA were coordinately repressed by 10(-7) M 1,25 (OH)2D3 in fetal bovine chondrocytes, but transcription, as determined by nuclear runoff assay, was not appreciably influenced in fetal bovine chondrocytes or in rat lung fibroblasts. Similarly, exposure to 1,25(OH)2D3 did not influence chloramphenicol acetyl-transferase activity expressed by a human tropoelastin promoter-expression construct in either cell type. Exposure to cycloheximide had little effect on tropoelastin mRNA levels in control cells but partially restored tropoelastin mRNA levels in cells pretreated with 1,25(OH)2D3 and prevented repression when added together with 1,25(OH)2D3. Similarly, simultaneous exposure to actinomycin D and 1,25(OH)2D3 attenuated the down-regulation of tropoelastin. These data indicate that repression of tropoelastin steady-state mRNA levels by 1,25(OH)2D3 is primarily mediated by a posttranscriptional mechanism that requires both transcription and protein synthesis for full effect.
Because 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has been shown to play roles in both proliferation and differentiation of novel target cells, the potential expression of 1,25(OH)2D3 receptor (VDR) activity was investigated in cultured bovine aortic endothelial cells (BAEC). Receptor binding assays performed on nuclear extracts of BAEC revealed a single class of specific, high-affinity VDR that displayed a 4.5-fold increase in maximal ligand binding (Nmax) in rapidly proliferating BAEC compared with confluent, density-arrested cells. When confluent BAEC were incubated with activators of protein kinase C (PKC), Nmax increased 2.5-fold within 6-24 h and this upregulation was prevented by sphingosine, an inhibitor of PKC, as well as by actinomycin D or cycloheximide. Immunohistochemical visualization using a specific MAb disclosed nuclear localized VDR in venular and capillary endothelial cells of human skin biopsies, documenting the expression of VDR, in vivo, and validating the BAEC model. Finally, additional experiments indicated that BAEC formed the 1,25(OH)2D3 hormonal metabolite from 25(OH)D3 substrate, in vitro, and growth curves of BAEC maintained in the presence of 10(-8) M 1,25(OH)2D3 showed a 36% decrease in saturation density. These data provide evidence for the presence of a vitamin D microendocrine system in endothelial cells, consisting of the VDR and a 1 alpha-hydroxylase enzyme capable of producing 1,25(OH)2D3. That both components of this system are coordinately regulated, and that BAEC respond to the 1,25(OH)2D3 hormone by modulating growth kinetics, suggests the existence of a vitamin D autocrine loop in endothelium that may play a role in the development and/or functions of this pathophysiologically significant cell population.
Previous studies have indicated that upon in vitro activation with mitogenic lectins, human peripheral blood T lymphocytes express receptors for the steroid hormone 1 alpha, 25-dihydroxyvitamin D3(1,25(OH)2D3). Furthermore, the hormone can inhibit interleukin 2 production by the activated cells. In this investigation, we report that human peripheral B lymphocytes activated in vitro with the B lymphotropic Epstein-Barr virus (EBV) also express 1,25(OH)2D3 receptor-like macromolecules. These receptors are localized in the cell nucleus and exhibit properties similar to those found in classical target tissues for 1,25(OH)2D3. They sediment on sucrose gradients at 3.3 S, display a dissociation constant (Kd) of 4 X 10(-10) M, and can bind to DNA. In addition to the 1,25(OH)2D3 receptors, however, EBV-activated lymphocytes express a second class of 1,25(OH)2D3-binding proteins that appear to occur mainly in the cell cytosol and exhibit distinct biochemical properties from the receptor, including higher sedimentation coefficients (3.7 S to 4 S) and the lack of ability to bind to DNA. The addition of 1,25(OH)2D3 to cultures of EBV-infected cells inhibited the production of IgM and IgG by the B cells. The vitamin D3 analog 24,25(OH)2D3 did not inhibit Ig production, thus suggesting that the effect is probably mediated through the high affinity receptor macromolecule localized in the nucleus. Because the EBV-induced Ig production is independent of T cell participation, the data also suggest that the effects of 1,25(OH)2D3 are exerted directly on the B cell. The present results add to the evidence of the importance of 1,25(OH)2D3 as an immunoregulatory hormone.
Vitamin D deficiency is now recognized as an epidemic in the United States. The major source of vitamin D for both children and adults is from sensible sun exposure. In the absence of sun exposure 1000 IU of cholecalciferol is required daily for both children and adults. Vitamin D deficiency causes poor mineralization of the collagen matrix in young children's bones leading to growth retardation and bone deformities known as rickets. In adults, vitamin D deficiency induces secondary hyperparathyroidism, which causes a loss of matrix and minerals, thus increasing the risk of osteoporosis and fractures. In addition, the poor mineralization of newly laid down bone matrix in adult bone results in the painful bone disease of osteomalacia. Vitamin D deficiency causes muscle weakness, increasing the risk of falling and fractures. Vitamin D deficiency also has other serious consequences on overall health and well-being. There is mounting scientific evidence that implicates vitamin D deficiency with an increased risk of type I diabetes, multiple sclerosis, rheumatoid arthritis, hypertension, cardiovascular heart disease, and many common deadly cancers. Vigilance of one's vitamin D status by the yearly measurement of 25-hydroxyvitamin D should be part of an annual physical examination.
Vitamin D deficiency is now recognized as an epidemic in the United States. The major source of vitamin D for both children and adults is from sensible sun exposure. In the absence of sun exposure 1000 IU of cholecalciferol is required daily for both children and adults. Vitamin D deficiency causes poor mineralization of the Collagen matrix in young children's bones leading to growth retardation and bone deformities known as rickets. In adults, vitamin D deficiency induces secondary hyperparathyroidism, which causes a loss of matrix and minerals, thus increasing the risk of osteoporosis and fractures. In addition, the poor mineralization of newly laid down bone matrix in adult bone results in the painful bone disease of osteomalacia. Vitamin D deficiency causes muscle weakness, increasing the risk of falling and fractures. Vitamin D deficiency also has other serious consequences on overall health and well-being. There is mounting scientific evidence that implicates vitamin D deficiency with an increased risk of type I diabetes, multiple sclerosis, rheumatoid arthritis, hypertension, cardiovascular heart disease, and many common deadly cancers. Vigilance of one's vitamin D status by the yearly measurement of 25-hydroxyvitamin D should be part of an annual physical examination.
Background: Vitamin D and calcium may affect the cardiovascular system independently and interactively. Purpose: To assess whether vitamin D and calcium supplements reduce the risk for cardiovascular events in adults. Data Sources: Studies published in English from 1966 to July 2009 in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. Study Selection: Two investigators independently selected 17 prospective studies and randomized trials that examined vitamin D supplementation, calcium supplementation, or both and subsequent cardiovascular events. Data Extraction: Three investigators extracted and checked data about study designs, participants, exposures or interventions, outcomes, and data quality. Data Synthesis: Five prospective studies of patients receiving dialysis and 1 study involving a general population showed consistent reductions in cardiovascular disease (CVD) mortality among adults who received vitamin D supplements. Four prospective studies of initially healthy persons found no differences in incidence of CVD between calcium supplement recipients and nonrecipients. Results of secondary analyses in 8 randomized trials showed a slight but statistically nonsignificant reduction in CVD risk (pooled relative risk, 0.90 [95% CI, 0.77 to 1.05]) with vitamin D supplementation at moderate to high doses (approximately 1000 IU/d) but not with calcium supplementation (pooled relative risk, 1.14 [CI, 0.92 to 1.41]), or a combination of vitamin D and calcium supplementation (pooled relative risk, 1.04 [CI, 0.92 to 1.18]) compared with placebo. Limitations: Only articles published in English that reported cardiovascular event outcomes were included. The small number of studies, the lack of trials designed specifically to assess primary effects on cardiovascular outcomes, and important between-study heterogeneity preclude definitive conclusions. Conclusion: Evidence from limited data suggests that vitamin D supplements at moderate to high doses may reduce CVD risk, whereas calcium supplements seem to have minimal cardiovascular effects. Further research is needed to elucidate the role of these supplements in CVD prevention.
Background:
Vitamin D (25-OH D3) deficiency represents a rising social and economic problem in Western countries. Vitamin D has been recently reported to modulate inflammatory processes, endothelium and smooth muscle cell proliferation and even platelet function, thus potentially modulating atherothrombosis. Great interest has been addressed on its impact on cardiovascular outcome, with contrasting results. The aim of current study was to evaluate the relationship between 25-OH D3 and the extent of coronary artery disease (CAD) in a consecutive cohort of patients undergoing coronary angiography.
Materials and methods:
Patients undergoing elective coronary angiography were included in a cross-sectional study. Fasting samples were collected for 25-OH D3 levels assessment. Significant CAD was defined as at least 1 vessel stenosis > 50%, while severe CAD as left main and/or trivessel disease, as evaluated by quantitative coronary angiography.
Results:
Hypovitaminosis D was observed in 70·4% of 1484 patients. Patients were divided according to vitamin D tertiles (< 9·6; 9·6-18·4; ≥ 18·4). Lower vitamin D levels were associated with age, female gender (P < 0·001), renal failure (P = 0·05), active smoking (P = 0·001), acute coronary syndrome at presentation (P < 0·001), therapy with calcium antagonists (P = 0·02) and diuretics (P < 0·001), less beta-blockers (P = 0·02) and statins (P = 0·001) use. Vitamin D was directly related to haemoglobin (P < 0·001) and inversely with platelet count (P = 0·002), total and low-density-lipoprotein cholesterol (P = 0·002 and P < 0·001) and triglycerides (P = 0·01). Vitamin D did not influence angiographic features of coronary lesions, but was associated with higher prevalence of left main or right CAD (P = 0·03). Vitamin D deficiency was significantly associated with higher prevalence of CAD (adjusted OR [95%CI] = 1·32[1·1-1·6], P = 0·004) and severe CAD (adjusted OR [95%CI] = 1·18[1-1·39], P = 0·05).
Conclusion:
Hypovitaminosis D was observed in the vast majority of patients undergoing coronary angiography. Vitamin D deficiency is significantly associated with the prevalence and extent of CAD, especially for patients with values < 10 ng/mL. Therefore, future large studies are needed to evaluate whether vitamin D supplementation may prevent CAD and its progression.
Platelets are activated by increased cytosolic Ca2+ concentration ([Ca2+]i) following store-operated calcium entry (SOCE) accomplished by calciumrelease-activated calcium (CRAC) channel moiety Orai1 and its regulator STIM1. In other cells, Ca2+ transport is regulated by 1,25(OH)2 vitamin D3 [1,25(OH) 2D3]. 1,25(OH)2D3 formation is inhibited by klotho and excessive in klotho-deficient mice (kl/kl). The present study explored the effect of klotho deficiency on platelet Ca2+ signaling and activation. Platelets and megakaryocytes isolated from WT and kl/kl-mice were analyzed by RT-PCR, Western blotting, confocal microscopy, Fura-2-fluorescence, patch clamp, flow cytometry, aggregometry, and flow chamber. STIM1/Orai1 transcript and protein levels, SOCE, agonist-induced [Ca2+]i increase, activation-dependent degranulation, integrin αIIbβ3 activation and aggregation, and thrombus formation were significantly blunted in kl/kl platelets (by 27-90%). STIM1/Orai1 transcript and protein levels, as well as CRAC currents, were significantly reduced in kl/kl megakaryocytes (by 38-73%) and 1,25(OH) 2D3-treated WT megakaryocytes. Nuclear NF-kB subunit p50/p65 abundance was significantly reduced in kl/kl-megakaryocytes (by 51-76%). Transfection with p50/p65 significantly increased STIM1/Orai1 transcript and protein levels in megakaryocytic MEG-01 cells (by 46-97%). Low-vitamin D diet (LVD) of kl/kl mice normalized plasma 1,25(OH)2D3 concentration and function of platelets and megakaryocytes. Klotho deficiency inhibits platelet Ca2+ signaling and activation, an effect at least partially due to 1,25(OH)2D3-dependent down-regulation of NF-kB activity and STIM1/Orai1 expression in megakaryocytes.
Vitamin D plays a classical hormonal role in skeletal health by regulating calcium and phosphorus metabolism. Vitamin D metabolites also have physiological functions in nonskeletal tissues, where local synthesis influences regulatory pathways via paracrine and autocrine mechanisms. The active metabolite of vitamin D, 1α,25-dihydroxyvitamin D, binds to the vitamin D receptor that regulates numerous genes involved in fundamental processes of potential relevance to cardiovascular disease, including cell proliferation and differentiation, apoptosis, oxidative stress, membrane transport, matrix homeostasis, and cell adhesion. Vitamin D receptors have been found in all the major cardiovascular cell types including cardiomyocytes, arterial wall cells, and immune cells. Experimental studies have established a role for vitamin D metabolites in pathways that are integral to cardiovascular function and disease, including inflammation, thrombosis, and the renin-angiotensin system. Clinical studies have generally demonstrated an independent association between vitamin D deficiency and various manifestations of degenerative cardiovascular disease including vascular calcification. However, the role of vitamin D supplementation in the management of cardiovascular disease remains to be established. This review summarizes the clinical studies showing associations between vitamin D status and cardiovascular disease and the experimental studies that explore the mechanistic basis for these associations.
Atherosclerosis, the principal cause of cardiovascular diseases (CVDs), is a process that involves a complex interplay among different factors and cell types, including cells of the immune system (T cells, B cells, natural killer cells, monocytes/macrophages, dendritic cells) and cells of the vessel wall (endothelial cells [ECs], vascular smooth muscle cells [VSMCs]). The atherogenic process evolves in different stages, starting from inflammatory endothelial activation/dysfunction and resulting in plaque vulnerability and rupture.1
Several cardiovascular risk factors have been recognized. Among them, vitamin D deficiency [25(OH)D <20 ng/mL] is emerging as a new one. In addition to its well-defined role in bone and calcium metabolism, vitamin D has been identified as an important factor in cardiovascular health.2–8
Vitamin D deficiency affects almost 50% of the population worldwide. It has been suggested that this pandemic might contribute to the worldwide increased prevalence of CVD.9–11
Several mechanisms have been proposed to account for this inverse relationship. In addition to its effects exerted on numerous tissues and organs that indirectly participate in the atherosclerosis, vitamin D is directly involved in this systemic inflammatory process.12,13 Vitamin D receptors (VDRs) are present in all cells implicated in atherosclerosis, including ECs, VSMCs, and immune cells. Vitamin D appears to regulate a wide range of physiological and pathological processes like vascular cell growth, migration, and differentiation; immune response modulation; cytokine expression; and inflammatory and fibrotic pathways, all of which play a crucial role, starting from the early stage of endothelial activation/dysfunction to the later stages of the plaque vulnerability and rupture.
In this review, we provide current data on the effects of vitamin D on cells directly implicated in atherosclerosis such as ECs, VSMCs, and immune cells (lymphocytes, monocytes, macrophages, etc) with a focus on the underlying molecular mechanisms, …
The vitamin D hormone 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) is essential for the preservation of serum calcium and phosphate levels, but may also be important for the regulation of cardiovascular function. Epidemiological data in humans have shown that vitamin D insufficiency is associated with hypertension, left ventricular hypertrophy, increased arterial stiffness, and endothelial dysfunction in normal subjects and in patients with chronic kidney disease and type 2 diabetes. However, the pathophysiological mechanisms underlying these associations remain largely unexplained. In this study we aimed to decipher the mechanisms how 1,25(OH)2D3 may regulate systemic vascular tone and cardiac function, using mice carrying a mutant, functionally inactive vitamin D receptor (VDR). To normalize calcium homeostasis in VDR mutant mice, we kept the mice lifelong on the so-called rescue diet enriched with calcium, phosphate, and lactose. Here, we report that VDR mutant mice are characterized by lower bioavailability of the vasodilator nitric oxide (NO) due to reduced expression of the key NO synthesizing enzyme, endothelial NO synthase (NOS3), leading to endothelial dysfunction, increased arterial stiffness, increased aortic impedance, structural remodeling of the aorta, and impaired systolic and diastolic heart function at later ages, independent of changes in the renin-angiotensin system. We further demonstrate that 1,25(OH)2D3 is a direct transcriptional regulator of NOS3. Our data demonstrate the importance of intact VDR signaling in the preservation of vascular function, and may provide a mechanistic explanation for epidemiological data in humans showing that vitamin D insufficiency is associated with hypertension and endothelial dysfunction.
A 56-year-old black female patient with significant coronary heart disease (CHD) after several percutaneous intervention procedures for acute coronary syndromes was seen in the office for routine follow-up. She is 5 ft 5 in tall and weighs 265 pounds. She had recently gained 25 pounds after losing nearly 100 pounds following bariatric surgery. Her blood pressure, which was previously controlled with her therapy for hypertension, which included a β-blocker, an angiotensin-converting enzyme inhibitor, a calcium blocker, and a diuretic, was 160/90 mm Hg. Her fasting glucose was 168 mg/dL, with a hemoglobin A1C of 8.4% on therapy for type 2 diabetes mellitus. She was experiencing severe myalgias, which made it difficult for her to exercise, so she discontinued her atorvastatin. Her fasting lipid profile was as follows: total cholesterol, 264 mg/dL; high-density lipoprotein, 42 mg/dL; triglycerides, 220 mg/dL; and low-density lipoprotein, 178 mg/dL. Her 25-hydroxyvitamin D [25(OH)D] level was severely low at 8 ng/mL.
There have been several nutrient fads over recent decades, including beta carotene, selenium, folic acid, and vitamins E and C, all of which failed to show benefit in multiple large, randomized, controlled trials and thus did not stand the test of time, at least in terms of major cardiovascular event reduction.1,2 Without question, vitamin D increases absorption of calcium, magnesium, and phosphorus and mobilizes calcium and phosphorus from bone. It is also clear that vitamin D deficiency adversely affects the musculoskeletal system, predisposing to rickets in children and osteomalacia and osteoporosis in adults. The potential role of vitamin D in the pathogenesis of statin-induced myopathy and myalgias is debatable, although currently it appears reasonable to use vitamin D supplementation in patients with such symptoms, especially if …
Context:
Public health authorities around the world recommend widely variable supplementation strategies for adults, whereas several professional organizations, including The Endocrine Society, recommend higher supplementation.
Methods:
We analyzed published randomized controlled clinical trials to define the optimal intake or vitamin D status for bone and extraskeletal health.
Conclusions:
The extraskeletal effects of vitamin D are plausible as based on preclinical data and observational studies. However, apart from the beneficial effects of 800 IU/d of vitamin D3 for reduction of falls in the elderly, causality remains yet unproven in randomized controlled trials (RCTs). The greatest risk for cancer, infections, cardiovascular and metabolic diseases is associated with 25-hydroxyvitamin D (25OHD) levels below 20 ng/mL. There is ample evidence from RCTs that calcium and bone homeostasis, estimated from serum 1,25-dihydroxyvitamin D and PTH, calcium absorption, or bone mass, can be normalized by 25OHD levels above 20 ng/mL. Moreover, vitamin D supplementation (800 IU/d) in combination with calcium can reduce fracture incidence by about 20%. Such a dose will bring serum levels of 25OHD above 20 ng/mL in nearly all postmenopausal women. Based on calculations of the metabolic clearance of 25OHD, a daily intake of 500-700 IU of vitamin D3 is sufficient to maintain serum 25OHD levels of 20 ng/mL. Therefore, the recommendations for a daily intake of 1500-2000 IU/d or serum 25OHD levels of 30 ng or higher for all adults or elderly subjects, as suggested by The Endocrine Society Task Force, are premature. Fortunately, ongoing RCTs will help to guide us to solve this important public health question.
Reduced monocyte infiltration into the vessel wall and increased macrophage cholesterol efflux are critical components in atherosclerotic plaque regression. During inflammation, monocyte chemotactic protein 1 (MCP-1) signaling activation and cholesterol deposition in macrophages induces endoplasmic reticulum (ER) stress, which promotes an increased inflammatory response. Increased macrophage ER stress shifts macrophages into an M2 macrophage phenotype with increased cholesterol uptake and deposition. In type 2 diabetes, a population with elevated baseline risk of cardiovascular disease (CVD), vitamin D deficiency doubles that risk. We have found that 1,25-dihydroxy vitamin D [1,25(OH)(2)D] prevents foam cell formation during macrophage differentiation by suppressing ER stress. However, it is unknown whether suppression of ER stress by 1,25(OH)(2)D decreases monocyte infiltration and reverses atherogenic cholesterol metabolism in previously-differentiated, vitamin D-deplete macrophages. We collected peripheral monocytes from type 2 diabetic patients and differentiated them into macrophages under vitamin D-deplete or 1,25(OH)(2)D-supplemented conditions. 1, 25(OH)(2)D supplementation suppressed macrophage migration in response to MCP-1 and mRNA expression of chemokine (C-C motif) receptor 2 (CCR2), the MCP-1 receptor, compared to vitamin D-deplete cells. Furthermore, inhibition of ER stress with phenyl butyric acid resulted in similar effects even in vitamin D-deplete cells, while induction of ER stress with Thapsigargin under 1,25(OH)(2)D-supplemented conditions increased macrophage migration and CCR2 expression, suggesting that the effects of vitamin D on migration are mediated through ER stress suppression. To determine whether the detrimental pattern of macrophage cholesterol metabolism in vitamin D depletion is reversible, we assessed cholesterol uptake in macrophages differentiated under vitamin D-deplete conditions as described above, then supplemented with 1,25(OH)(2)D or maintained in vitamin D-deplete conditions. Cholesterol uptake was decreased in 1,25(OH)(2)D-supplemented compared to vitamin D-deplete cells, suggesting slowed cholesterol deposition with active vitamin D. 1,25(OH)(2)D supplementation also suppressed cholesteryl ester formation and enhanced cholesterol efflux in M2 macrophages compared to vitamin D-deplete cells, suggesting facilitation of cholesterol egress in the presence of 1,25(OH)(2)D. We thus provide further evidence that active vitamin D is an ER stress reliever that may have a role in atherosclerotic plaque regression.