Figure - available via license: CC BY
Content may be subject to copyright.
Proposed mechanism of homocysteine associated hypertension in diabetes. Diabetes causes renal microvascular constriction and deposition of extracellular matrix in the glomerular basement membrane. This causes glomerulosclerosis and impaired glomerular function (GFR). Renal hypofiltration increases plasma homocysteine level, which further cause oxidative stress and amplifies glomerular injury. Increased matrix accumulation in the myocardium leads to deposition of extracellular matrix between endothelium and myocyte causing endothelium myocyte uncoupling. This causes prevention of NO to pass through the matrix barrier and impairs left ventricular diastolic dysfunction. Glomerulosclerosis and L-V diastolic dysfunction results in hypertension.

Proposed mechanism of homocysteine associated hypertension in diabetes. Diabetes causes renal microvascular constriction and deposition of extracellular matrix in the glomerular basement membrane. This causes glomerulosclerosis and impaired glomerular function (GFR). Renal hypofiltration increases plasma homocysteine level, which further cause oxidative stress and amplifies glomerular injury. Increased matrix accumulation in the myocardium leads to deposition of extracellular matrix between endothelium and myocyte causing endothelium myocyte uncoupling. This causes prevention of NO to pass through the matrix barrier and impairs left ventricular diastolic dysfunction. Glomerulosclerosis and L-V diastolic dysfunction results in hypertension.

Source publication
Article
Full-text available
Dysfunction of macro- and microvessels is a major cause of morbidity and mortality in patients with cardio-renovascular diseases such as atherosclerosis, hypertension, and diabetes. Renal failure and impairment of renal function due to vasoconstriction of the glomerular arteriole in diabetic nephropathy leads to renal volume retention and increase...

Citations

... Though there are mixed views concerning the link between Hcy and blood pressure [10,28,[37][38][39], various mechanisms in support of a positive association have been put forward [6,40,41]. Under conditions of HHcy, uptake and synthesis of cysteine (an essential precursor of gluthathione) is reduced and antioxidant potential compromised thus leading to oxidative stress [42]. ...
... Additionally, Hcy is also metabolised into Hcy-thiolactone, a reactive specie which when bound to collagen, inhibits its activity [7]. The resultant effect of these is endothelial damage, endothelium-myocyte uncoupling, hindered passage of nitric oxide through the matrix barrier, poor vasodilation, diastolic dysfunction and high blood pressure [6,40]. Other possible mechanisms include increased arterial stiffness, increased arteriolar constriction, increased sodium reabsorption, poor elastic vascular wall and smooth cell proliferation [6]. ...
Article
Full-text available
Background Evidence linking homocysteine (Hcy) with cardiovascular diseases (CVD) or its risk factors are limited in a sub-Saharan black population. Objective We set out to evaluate the association between Hcy and hypertension and other CVD risk factors in a population of adult Nigerians. Methods Data of 156 adults aged 18–70 years was accessed from the North Central study site of the REmoving the MAsk on Hypertension (REMAH) study. Homocysteine, blood glucose and lipid profile in whole blood/serum were measured using standard laboratory methods. Hypertension was diagnosed if average of 5 consecutive blood pressure (BP) measurements obtained using a mercury sphygmomanometer was equal to or higher than 140 systolic and/or 90 mmHg diastolic or the individual is on antihypertensive medication. Hyperhomocysteinemia (HHcy) was defined as Hcy > 10 µmol/L. Results Of the 156 participants, 72 (43.5%) were hypertensive, of whom 18 had HHcy. Subjects with HHcy were significantly (p < 0.05) older (41.5 vs. 40.6yrs), had lower HDL-cholesterol (0.6 vs. 0.8 mmol/L) and higher systolic (145.5 vs. 126.0 mmHg) and diastolic BP (92.9 vs. 79.6 mmHg), compared to those without HHcy. Intake of alcohol and a 1 yr increase in age were respectively and significantly (p < 0.05) associated with a 1.54 and 0.10 µmol/L increase in Hcy. In a multivariable model adjusted for age, sex and body mass index, a 1 µmol/L increase in Hcy, was associated with a 1.69 mmHg and 1.34 mmHg increase in systolic and diastolic pressure (p < 0.0001) respectively; and a 0.01 mmol/L decrease in HDL-cholesterol (p < 0.05). Conclusion HHcy occurs among hypertensive Nigerians and it is independently associated with age, HDL-cholesterol, systolic and diastolic BP.
... Indian patients with coronary heart disease, Mahalle and colleagues 28 Though there are mixed views concerning the link between Hcy and blood pressure 10,25,[33][34][35] , various mechanisms in support of a positive association have been put forward 6,36,37 . Under conditions of HHcy, uptake and synthesis of cysteine (an essential precursor of gluthathione) is reduced and antioxidant potential compromised thus leading to oxidative stress 38 . ...
... Additionally, Hcy is also metabolised into Hcy-thiolactone, a reactive specie which when bound to collagen, inhibits its activity 7 . The resultant effect of these is endothelial damage, endothelium-myocyte uncoupling, hindered passage of nitric oxide through the matrix barrier, poor vasodilation, diastolic dysfunction and high blood pressure 6,36 . ...
Preprint
Full-text available
Background: Evidence linking homocysteine (Hcy) with cardiovascular diseases (CVD) or its risk factors are insufficient in a Sub-Saharan black population. Objective: We set out to evaluate the association between Hcy and hypertension and other CVD risk factors in a population of adult Nigerians. Methods: Data of 156 adults aged 18-70years was accessed from the North Central study site of the REmoving the MAsk on Hypertension (REMAH) study. Homocysteine, blood glucose and lipid profile in whole blood/serum were measured using standard laboratory methods. Hypertension was diagnosed if average of 5 consecutive blood pressure (BP) measurements obtained using a mercury sphygmomanometer was equal to or higher than 140 systolic and/or 90 mmHg diastolic or the individual is on antihypertensive medication. Hyperhomocysteinemia (HHcy) was defined as Hcy>10µmol/L. Results: Of the 156 participants, 72 (43.5%) were hypertensive, of whom 18 had HHcy. Subjects with HHcy were significantly (p<0.05) older (41.5 vs 40.6yrs), had lower HDL-cholesterol (0.6 vs 0.8mmol/L) and higher systolic (145.5 vs 126.0mmHg) and diastolic BP (92.9 vs 79.6mmHg), compared to those without HHcy. Intake of alcohol and a 1yr increase in age were respectively and significantly (p<0.05) associated with a 1.54 and 0.10 µmol/L increase in Hcy. In a multivariable model adjusted for age, sex and body mass index, a 1µmol/L increase in Hcy, was associated with a 1.69 mmHg and 1.34 mmHg increase in systolic and diastolic pressure (p< 0.0001) respectively; and a 0.01mmol/L decrease in HDL-cholesterol (p<0.05). Conclusion: HHcy occurs among hypertensive Nigerians and it is independently associated with age, HDL-cholesterol, systolic and diastolic BP.
... [5,6,31] The possible mechanisms of vascular injury involve oxidative stress interfering with the balance of the nitric oxide synthase system, immune and inflammatory responses, dyslipidemia, and coagulation dysfunction. [33][34][35][36][37] A combination of multiple mechanisms eventually leads to the development of atherosclerosis and CVD. ...
Article
Full-text available
The influences of hyperhomocysteinemia on cardiovascular diseases (CVDs), stroke and new-onset hypertension are unclear. The aim of the study is to explore the associations of homocysteine levels with stroke, CVDs, and new-onset hypertension in Chinese individuals.This retrospective cohort study included outpatients and inpatients from the Department of Geriatrics at Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine from January to December 2000. They were divided based on their homocysteine (Hcy) levels in 2000: Q1 (<10 μmol/L), Q2 (10-15 μmol/L), and Q3 (>15 μmol/L) and according to whether they had hypertension at baseline. Information about stroke, mortality and major adverse cardiac events, and newly onset hypertension was gathered in December each year until 2017. The effects of Hcy levels on the risk for stroke and CVDs among all patients, and new-onset hypertension among patients without hypertension at baseline were evaluated.After adjustment for confounders, compared with the Q1 group (Hcy <10 μmol/L), when the Hcy increased to 10 to 15 μmol/L, the risks for stroke, CVDs, and new-onset hypertension significantly increased, and the hazard ratio and 95% confidence interval were 2.02 (1.35-3.05, P = .001), 2.22 (1.32-3.76, P = .003), and 7.20 (4.52-11.48, P < .001), respectively. Hcy improved the predictive capability of traditional risk factors for stroke. The optimal cut-off value of Hcy for predicting stroke was 13.4 μmol/L (sensitivity: 70.9%, specificity: 62.2%).Hcy 10 to 15 μmol/L is significantly associated with the risks for stroke, mortality and major adverse cardiac events, and hypertension. The best cut-off point of Hcy for predicting stroke is 13.4 μmol/L.
... The presence of the heterogeneity in these studies might be explained by the ethnicity of different regions and the coexistence of hypertension-related disease.71,[97][98][99][100][101][102][103][104][105][106] According to the fact that plasma Hcy could not only induce arteriolar constriction, increase sodium reabsorption, but also increase arterial stiffness,58,111 Hcy may beinvolved in the pathogenesis of hypertension. Our previous findings have demonstrated that the MTHFR C677T is significantly associated with childhood obesity, and a strong relationship between Hcy level and obesity was emphasized by virtue of MTHFR C677T polymorphism. ...
Article
Full-text available
Numerous researchers have investigated the associations among methylenetetrahydrofolate reductase gene (MTHFR) C677T polymorphism, homocysteine (Hcy) concentration, and hypertension. However, the results are controversial. Thus, a meta‐analysis implementing Mendelian randomization approach was conducted to examine the hypothesis that elevated Hcy concentration plausibly contributes to increased risk of hypertension. Based on several inclusion and exclusion criteria, eligible studies were selected to explore the correlation between MTHFR C677T and hypertension risk, MTHFR C677T and Hcy concentration in hypertension, and Hcy concentration and hypertension, and they were evaluated by odds ratios (ORs), effect size (ES), and standard mean difference with their corresponding 95% confidence intervals (95% CIs), respectively. Moreover, Mendelian randomization was implemented to evaluate the relationship between Hcy and hypertension. Consequently, 14 378 cases and 25 795 controls were involved in this study and the results showed that MTHFR C677T led to an elevated risk of hypertension (for T vs C: OR = 1.27, 95% CI = 1.17‐1.37; for TT vs CC: OR = 1.53, 95% CI = 1.30‐1.79). Additionally, in hypertensive subjects, the pooled Hcy concentration in individuals of TT genotype was 7.74 μmol/L (95% CI: 5.25‐10.23) greater than that in individuals of CC genotype. Moreover, the pooled Hcy concentration in hypertensive was 0.69 μmol/L (95% CI: 0.50‐0.87) greater than that in controls. The estimated causal OR associated with hypertension was 1.32 for 5 μmol/L Hcy increment. Via MTHFR C677T polymorphism, the findings in the present study demonstrated that there exists evidence on causal link between Hcy concentration and the risk of hypertension.
... However, the mechanisms by which homocysteine is thought to affect the vascular endothelium are consistent with in vitro research and known mechanisms for hypertension 3 . Hcy may play a role in the pathogenesis of hypertension is based on the fact that, Hcy induces arteriolar constriction, renal dysfunction and increased sodium reabsorption, increased arterial stiffness 4 . Hcy increases oxidative stress, which causes oxidative injury to the vascular endothelium, diminishing vasodilation by nitric oxide, stimulating proliferation of vascular smooth muscle cells and altering the elastic properties of the vascular wall, leading to hypertension 4 . ...
Article
Full-text available
An elevated serum homocysteine concentration is associated with an increased risk of coronary, cerebral, and peripheral vascular disease. The objective of the study was to evaluate the association of serum homocysteine level with hypertension (HTN). This cross sectional analytical study was conducted at Sir Salimullah Medical College & Mitford Hospital and National Health Care Network Dhaka, Bangladesh over a duration of 21 months from July 2012 to May 2014. Fifty HTN patients were included as study subjects and age and sex matched fifty non-HTN healtlhy controls were included. All the clinical measurements were taken and serum Hcy was measured for all study subjects. In this study, females were predominant in both groups, mean age of the HTN patients was 41.0±5.6 years and non-HTN healthy subjects was 38.2±5.2 years. BMI and FBG were found higher in HTN group than that of non-HTN group but the differences were not statistically significant. Systolic and diastolic BP were found significantly higher in HTN group than that of non-HTN group. Serum Hcy level was significantly higher in HTN group (19.93±4.12 μmol/L) than that of non-HTN group (13.20±1.88 μmol/L). This study depicted that serum Hcy had significant correlation with SBP and DBP in HTN. In conclusion, it was seen that elevated serum Hcy level is associated with hytpertension. Bangladesh J Med Biochem 2018; 11(1): 22-25
... ,46,47 Both conduit and resistance vessel endothelial function may be damaged by elevated Hcy levels,33 resulting in the development of hypertension.48 Female hormones, which have been established to have antioxidant effects that may reduce the risk based on Hcy, may be responsible for the observed differences.17,34,42 ...
Article
Full-text available
Plasma homocysteine (Hcy) levels are associated with elevated blood pressure. However, the causal association between Hcy levels and the risk of hypertension remains ambiguous. Taking the study design effect into consideration, this study aimed to investigate this issue through a cross‐sectional and longitudinal analysis. Data were obtained from the Beijing Health Management Cohort study, which conducted routine health check‐ups from 2012 to 2017. Multivariate logistic regression was used for the cross‐sectional analysis, and a quadratic inference function approach was performed for the longitudinal analysis. A total of 30 376 subjects (mean age = 50.0 years) were included in the cross‐sectional analysis, and a subgroup of 3913 subjects without hypertension at baseline was included in the longitudinal analysis. After adjusting for potential confounders, the risk of hypertension increased with Hcy levels in the cross‐sectional analysis using the traditional definition of hypertension (OR = 1.262, 95% CI: 1.155‐1.378, Q2 vs Q1; OR = 1.458, 95% CI: 1.335‐1.593, Q3 vs Q1; OR = 1.520, 95% CI: 1.388‐1.664, Q4 vs Q1) and the 2017 hypertension definition (OR = 1.159, 95% CI: 1.067‐1.259, Q2 vs Q1; OR = 1.328, 95% CI: 1.221‐1.445, Q3 vs Q1; OR = 1.328, 95% CI: 1.217‐1.449, Q4 vs Q1). The longitudinal analysis showed that hypertension risk increased in the third quartile of Hcy (OR = 1.268, 95% CI: 1.030‐1.560, Q3 vs Q1). Elevated total plasma Hcy may be used as a predictive biomarker for hypertension. Attention should be paid to gender‐specific mechanisms when issuing precise precautions.
... It has been implicated that the possible mechanisms that are involved in HHcy-mediated hypertension could be ROS-induced vascular endothelium damage that causes impairment in vasodilation, vascular remodeling with elastin degradation and collagen deposition and VSMC hyperproliferation [9,12]. A significant amount of other studies have also shown a positive correlation between Hcy plasma levels and hypertension [10,11,[67][68][69][70][71]. HHcy has been implicated to be involved in the initiation of vascular inflammation as one of the key mechanisms that contributes to the development of arterial vascular disease predisposing to hypertension [14,[72][73][74]. ...
Article
Full-text available
Although hyperhomocysteinemia (HHcy) is known to promote downstream pro-inflammatory cytokine elevation, the precise mechanism is still unknown. One of the possible receptors that could have significant attention in the field of hypertension is toll-like receptor 4 (TLR-4). TLR-4 is a cellular membrane protein that is ubiquitously expressed in all cell types of the vasculature. Its mutation can attenuate the effects of HHcy-mediated vascular inflammation and mitochondria- dependent cell death that suppresses hypertension. In this review, we observed that HHcy induces vascular remodeling through immunological adaptation, promoting inflammatory cytokine up-regulation (IL-1β, IL-6, TNF-α) and initiation of mitochondrial dysfunction leading to cell death and chronic vascular inflammation. The literature suggests that HHcy promotes TLR-4-driven chronic vascular inflammation and mitochondria-mediated cell death inducing peripheral vascular remodeling. In the previous studies, we have characterized the role of TLR-4 mutation in attenuating vascular remodeling in hyperhomocysteinemia. This review includes, but is not limited to, the physiological synergistic aspects of the downstream elevation of cytokines found within the vascular inflammatory cascade. These events subsequently induce mitochondrial dysfunction defined by excessive mitochondrial fission and mitochondrial apoptosis contributing to vascular remodeling followed by hypertension.
... However, they can be detrimental in breaking apart basement membrane contributing to ulcerations such as those observed in corneal tissue [17] . Over the last 30y our lab has been actively studying mechanisms that govern maintenance of tissues' structural integrity [18] , post-transcriptional regulation and metabolism of MMPs and TIMPs in human heart failure, atherosclerosis, microvascular permeability and vascular diseases [19][20][21][22][23][24] , involvement of MMPs in diabetes, hypertension, oxidative stress, nephropathy, and autophagy [25][26][27][28] . From our experience, we know that endogenous TIMPs regulate proteolytic activity by binding tightly to MMPs' active sites. ...
Article
Full-text available
There are many vision threatening diseases of the eye affecting millions of people worldwide. In this article, we are summarizing potential role of various matrix metalloproteinases (MMPs); the Zn (2+)-dependent endoproteases in eye health along with pathogenesis of prominent ocular diseases such as macular degeneration, diabetic retinopathy, and glaucoma via understanding MMPs regulation in affected patients, interactions of MMPs with their substrate molecules, and key regulatory functions of tissue inhibitor of metalloproteinases (TIMPs) towards maintaining overall homeostasis. © 2017, International Journal of Ophthalmology (c/o Editorial Office). All rights reserved.
... In relation to LV diastolic function, IVRT was reduced in the HB 6 group in relation to the CB6 and HcyT groups. This finding might be suggestive of diastolic dysfunction, probably by the HcyT effect of increased endothelial-myocyte uncoupling, resulting in hypertension 39 . E/A ratio was increased in the Hcy group compared to the CB 6 group. ...
... It has been implicated that the possible mechanisms that are involved in HHcy-mediated hypertension could be ROS-induced vascular endothelium damage that causes impairment in vasodilation, vascular remodeling with elastin degradation and collagen deposition and VSMC hyperproliferation [9,12]. A significant amount of other studies have also shown a positive correlation between Hcy plasma levels and hypertension [10,11,[67][68][69][70][71]. HHcy has been implicated to be involved in the initiation of vascular inflammation as one of the key mechanisms that contributes to the development of arterial vascular disease predisposing to hypertension [14,[72][73][74]. ...