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Jaume Padilla,
Nathan T Jenkins,
Sewon Lee,
Hanrui Zhang,
Jian Cui,
Mozow Yusof Zuidema, Cuihua Zhang,
Michael A Hill,
James W Perfield,
Jamal A Ibdah,
Frank W Booth,
J Wade Davis,
Maurice Harold Laughlin,
R Scott Rector
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ABSTRACT: We adopted a transcriptome-wide microarray analysis approach to determine the extent to which vascular gene expression is altered as a result of juvenile obesity and identify obesity-responsive mRNAs. We examined transcriptional profiles in the left anterior descending coronary artery (LAD), perivascular fat adjacent to the LAD, and descending thoracic aorta between obese (n=5) and lean (n=6) juvenile Ossabaw pigs (age=22 weeks). Obesity was experimentally induced by feeding the animals a high-fat/high fructose corn syrup/high-cholesterol diet for 16 weeks. We found that expression of 189 vascular cell genes in the LAD and expression of 165 genes in the thoracic aorta were altered with juvenile obesity (FDR≤10%) with an overlap of only 28 genes between both arteries. Notably, a number of genes found to be markedly up-regulated in the LAD of obese pigs are implicated in atherosclerosis, including ACP5, LYZ, CXCL14, APOE, PLA2G7, LGALS3, SPP1, ITGB2, CYBB, and P2RY12. Furthermore, pathway analysis revealed the induction of pro-inflammatory and pro-oxidant pathways with obesity primarily in the LAD. Gene expression in the LAD perivascular fat was minimally altered with juvenile obesity. Together, we provide new evidence that obesity produces artery-specific changes in pre-translational regulation with a clear up-regulation of pro-atherogenic genes in the LAD. Our data may offer potential viable drug targets and mechanistic insights regarding the molecular precursors involved in the origins of over-nutrition and obesity-associated vascular disease. In particular, our results suggest that the oxLDL-LOX-1-NFκB signaling axis may be involved in the early initiation of a juvenile obesity-induced pro-atherogenic coronary artery phenotype.
Physiological Genomics 04/2013; · 2.73 Impact Factor
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ABSTRACT: Key points Sedentary and high-fat diet lifestyles are associated with greater prevalence of obesity and type 2 diabetes in humans, both of which independently increase atherosclerosis. High-fat diet in sedentary individuals produces endothelial dysfunction in blood vessels as a first step toward coronary arteriosclerosis. We observed preservation of coronary arteriolar vascular function when mice began voluntary running in wheels at the start of a high-fat diet. We further showed that mechanisms by which running opposed the detrimental effects of high-fat diet on vascular function included maintenance of eNOS phosphorylation, leptin sensitivity, and redox balance in mouse coronary arterioles. The results provide evidence for how physical activity is an effective therapy to oppose the development of atherosclerosis in the first place.
The Journal of Physiology 06/2012; 590(Pt 17):4255-68. · 4.72 Impact Factor
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ABSTRACT: Adiponectin (APN) can confer protection against metabolism-related illnesses in organs such as fat, the liver, and skeletal muscle. However, it is unclear whether APN improves endothelial-dependent nitric oxide-mediated vasodilation in type 2 diabetes and, if so, by what mechanism. We tested whether exogenous APN delivery improves endothelial function in type 2 diabetic mice and explored the mechanisms underlying the observed improvement. To test the hypothesis, we injected adenovirus APN (Ad-APN) or adenovirus β-galactosidase (Ad-βgal; control virus) via the tail vein in control (m Lepr(db)) and diabetic (Lepr(db); db/db) mice and studied vascular function of the aorta ex vivo. Ad-APN improved endothelial-dependent vasodilation in db/db mice compared with Ad-βgal, whereas Ad-APN had no further improvement on endothelial function in control mice. This improvement was completely inhibited by a nitric oxide synthase inhibitor (N(G)-nitro-l-arginine methyl ester). Serum triglyceride and total cholesterol levels were increased in db/db mice, and Ad-APN significantly reduced triglyceride levels but not total cholesterol levels. Immunoblot results showed that interferon-γ, gp91(phox), and nitrotyrosine were markedly increased in the aorta of db/db mice. Ad-APN treatment decreased the expression of these proteins. In addition, mRNA expression of TNF-α, IL-6, and ICAM-1 was elevated in db/db mice, and Ad-APN treatment decreased these expressions in the aorta. Our findings suggest that APN may contribute to an increase in nitric oxide bioavailability by decreasing superoxide production as well as by inhibiting inflammation and adhesion molecules in the aorta in type 2 diabetic mice.
AJP Heart and Circulatory Physiology 05/2012; 303(1):H106-15. · 3.71 Impact Factor
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ABSTRACT: Vascular dysfunction contributes to the pathogenesis of various cardiovascular diseases. Dietary supplements, including fish oil, dietary fibers, and various natural products, and exercise training exert vasoprotective effects. However, the mechanisms underlying the vasoprotective benefits of dietary supplements and physical activity demand extensive investigation. Accumulating evidence suggests that inflammatory cytokine tumor necrosis factor-alpha (TNFα) plays a pivotal role in the dysregulation of macrovascular and microvascular function. TNFα induces vascular inflammation, monocyte adhesion to endothelial cells, vascular oxidative stress, apoptosis, and atherogenic response and participates in the regulation of thrombosis and coagulation through multiple signaling pathways involving NFκB, Sp1, activator protein 1, JNK, p38, STAT3, and so forth. Dietary supplements and exercise training decrease TNFα production and ameliorate TNFα-mediated pathological changes in vasculature. Thus, the inhibitory effects of dietary supplements and physical exercise on TNFα production and TNFα signaling may contribute to their vasoprotective properties.
Experimental Diabetes Research 01/2012; 2012:972679. · 1.20 Impact Factor
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ABSTRACT: Despite abundant clinical evidence linking metabolic abnormalities to diabetic vasculopathy, the molecular basis of individual susceptibility to diabetic vascular complications is still largely undetermined. Endothelial dysfunction in diabetes-associated vascular complications is considered an early stage of vasculopathy and has attracted considerable research interests. Type 2 diabetes is characterized by metabolic abnormalities, such as hyperglycemia, excess liberation of free fatty acids (FFA), insulin resistance and hyperinsulinemia. These abnormalities exert pathological impact on endothelial function by attenuating endothelium-mediated vasomotor function, enhancing endothelial apoptosis, stimulating endothelium activation/endothelium-monocyte adhesion, promoting an atherogenic response and suppressing barrier function. There are multiple signaling pathways contributing to the adverse effects of glucotoxicity on endothelial function. Insulin maintains the normal balance for release of several factors with vasoactive properties. Abnormal insulin signaling in the endothelium does not affect the whole-body glucose metabolism, but impairs endothelial response to insulin and accelerates atherosclerosis. Excessive level of FFA is implicated in the pathogenesis of insulin resistance. FFA induces endothelial oxidative stress, apoptosis and inflammatory response, and inhibits insulin signaling. Although hyperglycemia, insulin resistance, hyperinsulinemia and dyslipidemia independently contribute to endothelial dysfunction via various distinct mechanisms, the mutual interactions may synergistically accelerate their adverse effects. Oxidative stress and inflammation are predicted to be among the first alterations which may trigger other downstream mediators in diabetes associated with endothelial dysfunction. These mechanisms may provide insights into potential therapeutic targets that can delay or reverse diabetic vasculopathy.
Archiv für Kreislaufforschung 01/2012; 107(1):237. · 7.35 Impact Factor
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ABSTRACT: Type 2 diabetes (T2D) is a leading risk factor for cardiovascular diseases including atherosclerosis and coronary heart disease. Exercise training (ET) is thought to have a beneficial effect on these disorders, but the basis for this effect is not fully understood. Because endothelial dysfunction plays a key role in the pathological events leading to cardiovascular complications in T2D, we hypothesized that the effects of ET will be evidenced by improvements in coronary endothelial function. To test this hypothesis, we assessed the effects of ET on vascular function of diabetic (db/db, Lepr(db)) mice by evaluating endothelial function of isolated coronary arterioles of wild-type (WT) and db/db mice with/without ET. Although dilation of vessels to the endothelial-independent vasodilator, sodium nitroprusside was not different between db/db and WT, dilation to the endothelial-dependent agonist, acetylcholine (ACh), was impaired in db/db compared to WT mice. Vasodilation to ACh was restored in db/db with ET and insulin sensitivity was improved in the db/db after ET. Exercise did not change body weight of db/db, but superoxide dismutase (SOD1 and SOD2) and phosphorylated- eNOS protein (Ser1177) expression in heart tissue was up-regulated whereas tumor necrosis factor-alpha (TNF-α) protein level was decreased by ET. Serum level of interleukin-6 (IL-6) was higher in db/db mice but ET decreased IL-6. This suggests that ET may improve endothelial function by increasing nitric oxide bioavailability as well as decreasing chronic inflammation. We suggest this connection may be the basis for the benefit of ET in T2D.
American journal of biomedical sciences. 10/2011; 3(4):241-252.
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ABSTRACT: A multitude of factors, including increased coronary vascular resistance and dysregulated coronary microcirculatory function, contribute to the impairment of coronary blood flow (CBF) regulation and the pathogenesis of myocardial ischemia/reperfusion (I/R) injury. CBF is primarily determined by coronary vascular resistance, which is affected by the balance between various vasodilators and vasoconstrictors. Myocardial I/R causes reduced production of endogenous vasodilators, such as nitric oxide (NO), leaving unopposed vasoconstriction that is caused mainly by continued presence of endothelin-1 (ET-1) and serotonin (5-HT); this imbalance in turn enhances vascular tone, triggers inflammatory response, decreases CBF and exacerbates reperfusion injury. Various inflammatory cytokines participate in the regulation of coronary vasomotor function by affecting the balance between vasodilators and vasoconstrictors. In addition to the enhanced coronary vasoconstriction, coronary microembolization, inflammatory cell infiltration and post-ischemic hyperpermeability contribute to the impairment of coronary microcirculatory function and myocardial perfusion during I/R. Ongoing research examining the role of inflammation in the regulation of CBF and coronary microcirculatory function in myocardial I/R is expected to yield new insights that will lead to therapies for ameliorating the vascular inflammatory response in coronary artery diseases (CADs) in the clinical setting. This article is part of a Special Issue entitled "Coronary Blood Flow".
Journal of Molecular and Cellular Cardiology 09/2011; 52(4):865-72. · 5.17 Impact Factor
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ABSTRACT: Interferon-gamma (IFNγ) has previously been associated with immuno-mediated inflammation in diet-induced obesity and type 1 diabetes. This study sought to define the role of IFNγ-induced adipose tissue inflammation in endothelial dysfunction in type 2 diabetes. We examined mesenteric adipose tissue (MAT) inflammation, and endothelial function of small mesenteric artery (SMA) in control mice (m Lepr(db)), diabetic mice (Lepr(db)), m Lepr(db) treated with IFNγ, and Lepr(db) treated with anti-IFNγ or anti-monocyte chemoattractant protein-1 (anti-MCP-1). mRNA and protein expression of IFNγ and MCP-1 were increased in MAT of Lepr(db), accompanied by increased T-lymphocyte and macrophage infiltration. Anti-IFNγ reduced MAT inflammatory cell infiltration and inflammatory cytokine expression in Lepr(db), while IFNγ treatment showed the opposite effects in m Lepr(db). Acetylcholine (ACh)-induced vasorelaxation of SMA was impaired in Lepr(db) versus m Lepr(db), but sodium nitroprusside (SNP)-induced vasorelaxation was comparable. Both anti-IFNγ and anti-MCP-1 improved endothelial function of Lepr(db), while IFNγ treatment impaired endothelial function of m Lepr(db). Superoxide production was higher in both MAT and SMA of Lepr(db) mice, and anti-IFNγ reduced MAT and SMA superoxide production. Macrophage accumulation in the adventitia of SMA, and mRNA expression of MCP-1 in SMA were increased in Lepr(db) and IFNγ-treated m Lepr(db), but reduced in anti-IFNγ treated Lepr(db). These findings suggest IFNγ has a key role in the regulation of visceral adipose tissue inflammatory response and endothelial dysfunction in type 2 diabetes.
Archiv für Kreislaufforschung 08/2011; 106(6):1135-45. · 7.35 Impact Factor
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ABSTRACT: Bariatric surgery is emerging as an effective method to alleviate a multitude of medical conditions associated with morbid obesity and type 2 diabetes. However, little is known about the effects and mechanisms of bariatric surgery on visceral fat inflammation and endothelial dysfunction in type 2 diabetes. We hypothesize that bariatric surgery ameliorates interferon-γ-mediated adipose tissue inflammation/oxidative stress and improves endothelial function in type 2 diabetic mice.
Control mice (m Lepr(db)) and diabetic mice (Lepr(db)) were treated with either sham surgery or improved gastric bypass surgery and then were evaluated at 5, 10, 20, and 30 days to assess postsurgical effects. Surgery reduced body weight, abdominal adiposity, blood glucose level, and food intake in Lepr(db). The surgery-induced decrease in visceral adiposity was accompanied by amelioration of T-lymphocytes and macrophage infiltration, as well as reduction in the expression of interferon-γ and other inflammatory cytokines in the mesenteric adipose tissue (MAT) of Lepr(db) mice. Furthermore, surgery improved endothelium-dependent, but not endothelium-independent, vasorelaxation in small mesenteric arteries (SMA) of Lepr(db) mice. The improvement in endothelial function was largely attenuated by nitric oxide synthase inhibitor (L-NAME) incubation. Interferon-γ treatment increased the mRNA expression of tumor necrosis factor-α in the MAT of control mice and incubation of SMA of control mice with tumor necrosis factor-α caused impairment of endothelial function. Superoxide production in MAT/SMA and nitrotyrosine protein level in SMA were elevated in diabetic mice. Surgery reduced MAT/SMA oxidative stress in Lepr(db) mice.
The amelioration of adipose tissue inflammation and the improvement of endothelial function may represent important mechanisms that result in cardiovascular benefits after bariatric surgery.
Arteriosclerosis Thrombosis and Vascular Biology 06/2011; 31(9):2063-9. · 6.37 Impact Factor
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ABSTRACT: Type 2 diabetes (T2D) is a leading risk factor for a variety of cardiovascular diseases including coronary heart disease and atherosclerosis. Exercise training (ET) has a beneficial effect on these disorders, but the basis for this effect is not fully understood. This study was designed to investigate whether the ET abates endothelial dysfunction in the aorta in T2D. Heterozygous controls (m Lepr(db)) and type 2 diabetic mice (db/db; Lepr(db)) were either exercise entrained by forced treadmill exercise or remained sedentary for 10 wk. Ex vivo functional assessment of aortic rings showed that ET restored acetylcholine-induced endothelial-dependent vasodilation of diabetic mice. Although the protein expression of endothelial nitric oxide synthase did not increase, ET reduced both IFN-γ and superoxide production by inhibiting gp91(phox) protein levels. In addition, ET increased the expression of adiponectin (APN) and the antioxidant enzyme, SOD-1. To investigate whether these beneficial effects of ET are APN dependent, we used adiponectin knockout (APNKO) mice. Indeed, impaired endothelial-dependent vasodilation occurred in APNKO mice, suggesting that APN plays a central role in prevention of endothelial dysfunction. APNKO mice also showed increased protein expression of IFN-γ, gp91(phox), and nitrotyrosine but protein expression of SOD-1 and -3 were comparable between wild-type and APNKO. These findings in the aorta imply that APN suppresses inflammation and oxidative stress in the aorta, but not SOD-1 and -3. Thus ET improves endothelial function in the aorta in T2D via both APN-dependent and independent pathways. This improvement is due to the effects of ET in inhibiting inflammation and oxidative stress (APN-dependent) as well as in improving antioxidant enzyme (APN-independent) performance in T2D.
AJP Heart and Circulatory Physiology 05/2011; 301(2):H306-14. · 3.71 Impact Factor
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ABSTRACT: Stem cells possessing the potential to replace damaged myocardium with functional myocytes have drawn increasing attention in the past decade in treating ischemic heart diseases; these diseases are the leading cause of morbidity and mortality in the world. The adult heart has recently been shown to contain a few cardiac stem cells (CSCs) that, in theory, suggest cardiac repair following acute myocardial infarction is possible if the CSC titer could be increased. Stem cell-based therapies, including hematopoietic stem cells and mesenchymal stem cells, were proven to be marginal and transitional. Multiple factors and mechanisms, rather than direct cardiac regeneration are involved in stem cell-mediated cardiac functional improvement. This review will focus on (1) the interaction between inflammation and stem cells; (2) the fate of stem cells at the microcirculatory level, and their subsequent influences on stem cell-based therapies.
Archiv für Kreislaufforschung 03/2011; 106(3):317-24. · 7.35 Impact Factor
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Cuihua Zhang
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ABSTRACT: Our research focuses on microphysiological aspects of the cardiovascular system, with an emphasis on what is occurring in heart tissues, to learn more about how various diseases arise and how they can be avoided or cured. These diseases include atherosclerosis, diabetes, myocardial infarction, obesity and ischemia/reperfusion (I/R). We use animal models, particularly mice, to aid us in these studies. A key feature of our work centers on dissection of coronary arterioles and examining their functionality using drugs, electrophysiology, fluoroscopy, genomics, proteomics, and standard chemical analyses to determine their physiological status, and compare it with other treated animals. My laboratory is focusing on anti-inflammatory and antioxidative stress therapeutic effects, the roles of sodium salicylate, exercise and resveratrol in type 2 diabetes, I/R injury, obesity, and atherosclerosis. Recently, we began investigations of the effects of stem cells and gastric bypass surgery on vascular dysfunction in obesity and diabetes. Our work identifies how diet, exercise, surgical interventions and drugs can be considered to combat these diseases in a clinical setting.
World journal of cardiology. 02/2011; 3(2):59-64.
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ABSTRACT: Oxidized low-density lipoprotein (OxLDL) causes impairment of endothelium-dependent, nitric oxide (NO)-mediated vasodilation involving l-arginine deficiency. However, the underlying mechanism remains elusive. Since arginase and endothelial NO synthase (eNOS) share the substrate l-arginine, we hypothesized that OxLDL may reduce l-arginine availability to eNOS for NO production, and thus vasodilation, by up-regulating arginase. To test this hypothesis, porcine subepicardial arterioles (70-130 μm) were isolated for vasomotor study and for immunohistochemical detection of arginase and eNOS expressions. The coronary arterioles dilated dose-dependently to the endothelium-dependent NO-mediated vasodilator serotonin. This vasodilation was inhibited in the same manner by NOS inhibitor N(G)-nitro-l-arginine methyl ester and by lumenal OxLDL (0.5 mg protein/mL). The inhibitory effect of OxLDL was reversed after treating the vessels with either l-arginine (3 mM) or arginase inhibitor difluoromethylornithine (DFMO; 0.4 mM). Consistent with vasomotor alterations, OxLDL inhibited serotonin-induced NO release from coronary arterioles and this inhibition was reversed by DFMO. Vascular arginase activity was significantly elevated by OxLDL. Immunohistochemical analysis indicated that OxLDL increased arginase I expression in the vascular wall without altering eNOS expression. Taken together, these results suggest that OxLDL up-regulates arginase I, which contributes to endothelial dysfunction by reducing l-arginine availability to eNOS for NO production and thus vasodilation.
Microcirculation (New York, N.Y.: 1994) 01/2011; 18(1):36-45. · 2.37 Impact Factor
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Zoltan Ungvari,
Lora Bailey-Downs,
Tripti Gautam,
Rosario Jimenez,
Gyorgy Losonczy, Cuihua Zhang,
Praveen Ballabh,
Fabio A Recchia,
Donald C Wilkerson,
William E Sonntag,
Kevin Pearson,
Rafael de Cabo,
Anna Csiszar
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ABSTRACT: Hyperglycemia in diabetes mellitus promotes oxidative stress in endothelial cells, which contributes to development of cardiovascular diseases. Nuclear factor erythroid 2-related factor-2 (Nrf2) is a transcription factor activated by oxidative stress that regulates expression of numerous reactive oxygen species (ROS) detoxifying and antioxidant genes. This study was designed to elucidate the homeostatic role of adaptive induction of Nrf2-driven free radical detoxification mechanisms in endothelial protection under diabetic conditions. Using a Nrf2/antioxidant response element (ARE)-driven luciferase reporter gene assay we found that in a cultured coronary arterial endothelial cell model hyperglycemia (10-30 mmol/l glucose) significantly increases transcriptional activity of Nrf2 and upregulates the expression of the Nrf2 target genes NQO1, GCLC, and HMOX1. These effects of high glucose were significantly attenuated by small interfering RNA (siRNA) downregulation of Nrf2 or overexpression of Keap-1, which inactivates Nrf2. High-glucose-induced upregulation of NQO1, GCLC, and HMOX1 was also prevented by pretreatment with polyethylene glycol (PEG)-catalase or N-acetylcysteine, whereas administration of H(2)O(2) mimicked the effect of high glucose. To test the effects of metabolic stress in vivo, Nrf2(+/+) and Nrf2(-/-) mice were fed a high-fat diet (HFD). HFD elicited significant increases in mRNA expression of Gclc and Hmox1 in aortas of Nrf2(+/+) mice, but not Nrf2(-/-) mice, compared with respective standard diet-fed control mice. Additionally, HFD-induced increases in vascular ROS levels were significantly greater in Nrf2(-/-) than Nrf2(+/+) mice. HFD-induced endothelial dysfunction was more severe in Nrf2(-/-) mice, as shown by the significantly diminished acetylcholine-induced relaxation of aorta of these animals compared with HFD-fed Nrf2(+/+) mice. Our results suggest that adaptive activation of the Nrf2/ARE pathway confers endothelial protection under diabetic conditions.
AJP Heart and Circulatory Physiology 01/2011; 300(4):H1133-40. · 3.71 Impact Factor
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ABSTRACT: Excessive oxidative stress and low-grade chronic inflammation are major pathophysiological factors contributing to the development of cardiovascular diseases (CVD) such as hypertension, diabetes and atherosclerosis. Accumulating evidence suggests that a compromised anti-oxidant system can lead to excessive oxidative stress in cardiovascular related organs, resulting in cell damage and death. In addition, increased circulating levels of pro-inflammatory cytokines, such as tumor necrosis factor α, interleukin-6 and C-reactive protein, are closely related to morbidity and mortality of cardiovascular complications. Emerging evidence suggests that interventions including nutrition, pharmacology and exercise may activate expression of cellular anti-oxidant systems via the nuclear factor erythroid 2-related factor 2-Kelch-like ECH-associated protein 1 signaling pathway and play a role in preventing inflammatory processes in CVD. The focus of the present review is to summarize recent evidence showing the role of these anti-oxidant and anti-inflammatory interventions in cardiovascular disease. We believe that these findings may prompt new effective pathogenesis-oriented interventions, based on the exercise-induced protection from disease in the cardiovascular system, aimed at targeting oxidant stress and inflammation.
World journal of cardiology. 01/2011; 3(1):18-24.
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ABSTRACT: In addition to its role as a barrier between blood and tissues, the vascular endothelium is responsible for the synthesis and released of a number of vasodilators including prostaglandins, nitric oxide and endothelium-derived hyperpolarizing factor (EDHF). As one of these vasodilators, the specific nature of EDHF has not been fully elucidated, although a number of roles have been proposed. Importantly, many conditions, such as hypertension, hyperlipidemia, heart failure, ischemia-reperfusion and diabetes mellitus comprise vascular endothelial dysfunction with EDHF dysregulation. This article reviews reports on the role of EDHF in diabetes-related endothelial dysfunction.
World journal of cardiology. 01/2011; 3(1):25-31.
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12/2010; , ISBN: 9780470650714
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ABSTRACT: Reactive oxygen species (ROS) have long been proposed to be mediators of experimental cardiovascular pathology. There is also a wealth of data indicating that ROS are involved in clinical cardiovascular pathology. However, multiple clinical studies have shown little benefit from anti-oxidant treatments, whereas nearly all experimental studies have shown a marked effect of anti-oxidant therapy. One reason for this discrepancy is that ROS are produced through multiple different mechanisms of which some are clinically beneficial; thus, in a defined experimental system where predominately pathological ROS are generated does not mimic a clinical setting where there are likely to be multiple ROS generating systems producing beneficial and pathological ROS. Simple inhibition of ROS would not be expected to have the same result in these two situations; ergo, it is important to understand the molecular mechanism underlying the production of ROS so that clinical treatments can be tailored to target the pathological production of ROS. One such example of this in cardiovascular biology is tissue specific inflammation-mediated ROS generation. This and the following series of articles discuss the current understanding of the role of ROS in cardiovascular disease, specifically focusing on the molecular mechanisms of ROS generation and the actions of ROS within the cardiovascular system. Although there are still many areas with regard to the effects of ROS in the cardiovascular system that are not completely understood, there is a wealth of data suggesting that blocking pathological ROS production is likely to have beneficial clinical effects compared to traditional anti-oxidants.
World journal of cardiology. 12/2010; 2(12):408-10.
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ABSTRACT: Endothelial progenitor cells (EPCs) are a heterogeneous population of cells that are provided by the bone marrow and other adult tissue in both animals and humans. They express both hematopoietic and endothelial surface markers, which challenge the classic dogma that the presumed differentiation of cells into angioblasts and subsequent endothelial and vascular differentiation occurred exclusively in embryonic development. This breakthrough stimulated research to understand the mechanism(s) underlying their physiologic function to allow development of new therapeutic options. One focus has been on their ability to form new vessels in injured tissues, and another has been on their ability to repair endothelial damage and restore both monolayer integrity and endothelial function in denuded vessels. Moreover, measures of their density have been shown to be a better predictor of cardiovascular events, both in healthy and coronary artery disease populations than the classical tools used in the clinic to evaluate the risk stratification. In the present paper we review the effects of EPCs on revascularization and endothelial repair in animal models and human studies, in an attempt to better understand their function, which may lead to potential advancement in clinical management.
World journal of cardiology. 12/2010; 2(12):411-20.
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Obesity 11/2010; 18(11):2071-6. · 4.28 Impact Factor
