stilbenes and Coronary-Artery-Disease

Ischemic heart disease is a leading cause of cardiac dysfunction and subsequent morbidity and mortality around the world. New therapies are required to complement or enhance the existing treatment regimen for the management of ischemic heart disease-related clinical complications. In this regard, compounds derived from natural sources have recently gained attention for their cardioprotective properties. In particular, the potential of food-derived compounds that exhibit medicinal properties (termed nutraceuticals) appears promising, an example being the plant polyphenol resveratrol. In the past two decades, many preclinical and a few pilot clinical studies have shown that resveratrol is beneficial in protecting against cardiovascular disease. In this short review, we will discuss current evidence on the efficacy of resveratrol in preventing or reversing deleterious effects on the heart in the setting of ischemic heart disease.

Topics: Animals; Cardiotonic Agents; Coronary Artery Disease; Genetic Therapy; Humans; Myocardial Reperfusion Injury; Resveratrol; Stilbenes

Resveratrol is a polyphenolic compound found in red wine that is believed to be responsible for its beneficial cardiovascular effects. Extensive research in the past several decades has identified multiple mechanisms by which resveratrol modifies the cardiovascular risk factors that lead to coronary artery disease, yet translation to the clinical arena has been unexpectedly slow. In this article, we review the existing evidence regarding the beneficial effects of resveratrol and briefly discuss its potential therapeutic applications.

Topics: Animals; Cardiovascular System; Coronary Artery Disease; Humans; Lipid Peroxidation; Lipids; Macrophages; Metabolic Syndrome; Muscle, Smooth, Vascular; Myocardial Reperfusion; Plaque, Atherosclerotic; Resveratrol; Stilbenes; Thrombosis; Wine

The term FRENCH PARADOX was coined in 1992 to describe the relatively low incidence of cardiovascular disease in the French population, despite a relatively high dietary intake of saturated fats, and potentially attributable to the consumption of red wine. After nearly 20 years, several studies have investigated the fascinating, overwhelmingly positive biological and clinical associations of red wine consumption with cardiovascular disease and mortality. Light to moderate intake of red wine produces a kaleidoscope of potentially beneficial effects that target all phases of the atherosclerotic process, from atherogenesis (early plaque development and growth) to vessel occlusion (flow-mediated dilatation, thrombosis). Such beneficial effects involve cellular signaling mechanisms, interactions at the genomic level, and biochemical modifications of cellular and plasma components. Red wine components, especially alcohol, resveratrol, and other polyphenolic compounds, may decrease oxidative stress, enhance cholesterol efflux from vessel walls (mainly by increasing levels of high-density lipoprotein cholesterol), and inhibit lipoproteins oxidation, macrophage cholesterol accumulation, and foam-cell formation. These components may also increase nitric oxide bioavailability, thereby antagonizing the development of endothelial dysfunction, decrease blood viscosity, improve insulin sensitivity, counteract platelet hyperactivity, inhibit platelet adhesion to fibrinogen-coated surfaces, and decrease plasma levels of von Willebrand factor, fibrinogen, and coagulation factor VII. Light to moderate red wine consumption is also associated with a favorable genetic modulation of fibrinolytic proteins, ultimately increasing the surface-localized endothelial cell fibrinolysis. Overall, therefore, the "French paradox" may have its basis within a milieu containing several key molecules, so that favorable cardiovascular benefits might be primarily attributable to combined, additive, or perhaps synergistic effects of alcohol and other wine components on atherogenesis, coagulation, and fibrinolysis. Conversely, chronic heavy alcohol consumption and binge drinking are associated with increased risk of cardiovascular events. In conclusion, although mounting evidence strongly supports beneficial cardiovascular effects of moderate red wine consumption (one to two drinks per day; 10-30 g alcohol) in most populations, clinical advice to abstainers to initiate daily alcohol consumption h

Topics: Alcohol Drinking; Antioxidants; Atherosclerosis; Blood Pressure; Cardiovascular Diseases; Cholesterol, HDL; Coronary Artery Disease; Endothelium, Vascular; Fibrinolysis; Hemostasis; Humans; Resveratrol; Stilbenes; Wine

Numerous studies have shown that resveratrol (RES) exerts anti-inflammatory effects but human trials evidencing these effects in vivo are limited. Furthermore, the molecular mechanisms triggered in humans following the oral intake of RES are not yet understood. Therefore, the purpose of this study was to investigate the molecular changes in peripheral blood mononuclear cells (PBMCs) associated to the one-year daily intake of a RES enriched (8 mg) grape extract (GE-RES) in hypertensive male patients with type 2 diabetes mellitus (T2DM). We used microarrays and RT-PCR to analyze expression changes in genes and microRNAs (miRs) involved in the inflammatory response modulated by the consumption of GE-RES in comparison to a placebo and GE lacking RES. We also examined the changes in several serobiochemical variables, inflammatory and fibrinolytic markers. Our results showed that supplementation with GE or GE-RES did not affect body weight, blood pressure, glucose, HbA1c or lipids, beyond the values regulated by gold standard medication in these patients. We did not find either any significant change on serum inflammatory markers except for a significant reduction of ALP and IL-6 levels. The expression of the pro-inflammatory cytokines CCL3, IL-1β and TNF-α was significantly reduced and that of the transcriptional repressor LRRFIP-1 increased in PBMCs from patients taking the GE-RES extract. Also, a group of miRs involved in the regulation of the inflammatory response: miR-21, miR-181b, miR-663, miR-30c2, miR-155 and miR-34a were found to be highly correlated and altered in the group consuming the GE-RES for 12 months. Our results provide preliminary evidence that long-term supplementation with a grape extract containing RES downregulates the expression of key pro-inflammatory cytokines with the involvement of inflammation-related miRs in circulating immune cells of T2DM hypertensive medicated patients and support a beneficial immunomodulatory effect in these patients.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Coronary Artery Disease; Cytokines; Diabetes Mellitus, Type 2; Dietary Supplements; Gene Expression Regulation; Humans; Hypertension; Inflammation; Leukocytes, Mononuclear; Male; MicroRNAs; Middle Aged; Models, Molecular; Plant Extracts; Resveratrol; Stilbenes; Transcriptome; Vitis

The grape and wine polyphenol resveratrol exerts cardiovascular benefits but evidence from randomized human clinical trials is very limited. We investigated dose-depending effects of a resveratrol-containing grape supplement on stable patients with coronary artery disease (CAD) treated according to currently accepted guidelines for secondary prevention of cardiovascular disease.. In a triple-blind, randomized, placebo-controlled, one-year follow-up, 3-arm pilot clinical trial, 75 stable-CAD patients received 350 mg/day of placebo, resveratrol-containing grape extract (grape phenolics plus 8 mg resveratrol) or conventional grape extract lacking resveratrol during 6 months, and a double dose for the following 6 months. Changes in circulating inflammatory and fibrinolytic biomarkers were analyzed. Moreover, the transcriptional profiling of inflammatory genes in peripheral blood mononuclear cells (PBMCs) was explored using microarrays and functional gene expression analysis.. After 1 year, in contrast to the placebo and conventional grape extract groups, the resveratrol-containing grape extract group showed an increase of the anti-inflammatory serum adiponectin (9.6 %, p = 0.01) and a decrease of the thrombogenic plasminogen activator inhibitor type 1 (PAI-1) (-18.6 %, p = 0.05). In addition, 6 key inflammation-related transcription factors were predicted to be significantly activated or inhibited, with 27 extracellular-space acting genes involved in inflammation, cell migration and T-cell interaction signals presenting downregulation (p < 0.05) in PBMCs. No adverse effects were detected in relation to the study products.. Chronic daily consumption of a resveratrol-containing grape nutraceutical could exert cardiovascular benefits in stable-CAD patients treated according to current evidence-based standards, by increasing serum adiponectin, preventing PAI-1 increase and inhibiting atherothrombotic signals in PBMCs.

Topics: Adiponectin; Anti-Inflammatory Agents; Coronary Artery Disease; Dietary Supplements; Down-Regulation; Female; Humans; Leukocytes, Mononuclear; Male; Middle Aged; Plant Extracts; Research Design; Resveratrol; Stilbenes; Transcription Factors; Treatment Outcome; Vitis

Several beneficial effects of resveratrol (RES), a natural antioxidant present in red wine have already been described. The aim of our study was to investigate if RES had a clinically measurable cardioprotective effect in patients after myocardial infarction. In this double-blind, placebo controlled trial 40 post-infarction Caucasian patients were randomized into two groups. One group received 10 mg RES capsule daily for 3 months. Systolic and diastolic left ventricular function, flow-mediated vasodilation (FMD), several laboratory and hemorheological parameters were measured before and after the treatment. Left ventricular ejection fraction showed an increasing tendency (ns) by RES treatment. However, left ventricular diastolic function was improved significantly (p < 0.01) by RES. A significant improvement in endothelial function measured by FMD was also observed (p < 0.05). Low-density lipoprotein (LDL) level significantly decreased (p < 0.05) in the RES treated group. Red blood cell deformability decreased and platelet aggregation increased significantly in the placebo group (p < 0.05), while resveratrol treatment has prevented these unfavourable changes. Concerning other measured parameters no significant changes were observed neither in placebo nor in RES group. Our results show that resveratrol improved left ventricle diastolic function, endothelial function, lowered LDL-cholesterol level and protected against unfavourable hemorheological changes measured in patients with coronary artery disease (CAD).

Topics: Aged; Antioxidants; Brachial Artery; Coronary Artery Disease; Double-Blind Method; Endothelium, Vascular; Erythrocyte Deformability; Female; Humans; Male; Myocardial Infarction; Placebos; Platelet Aggregation; Resveratrol; Stilbenes; Vasodilation; Ventricular Function, Left

Microvascular complications are now recognized to play a major role in diabetic complications, and understanding the mechanisms is critical. Endothelial dysfunction occurs early in the course of the development of complications; the precise mechanisms remain poorly understood. Mitochondrial dysfunction may occur in a diabetic rat heart and may act as a source of the oxidative stress. However, the role of endothelial cell-specific mitochondrial dysfunction in diabetic vascular complications is poorly studied. Here, we studied the role of diabetes-induced abnormal endothelial mitochondrial function and the resultant endothelial dysfunction. Understanding the role of endothelial mitochondrial dysfunction in diabetic vasculature is critical in order to develop new therapies. We demonstrate that hyperglycaemia leads to mitochondrial dysfunction in microvascular endothelial cells, and that mitochondrial inhibition induces endothelial dysfunction. Additionally, we show that resveratrol acts as a protective agent; resveratrol-mediated mitochondrial protection may be used to prevent long-term diabetic cardiovascular complications.

Topics: Animals; Blood Glucose; Cell Movement; Cell Proliferation; Cells, Cultured; Coronary Artery Disease; Coronary Circulation; Coronary Vessels; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Endothelial Cells; Humans; Isolated Heart Preparation; Male; Microcirculation; Microvessels; Mitochondria; Myocardial Contraction; Rats, Sprague-Dawley; Resveratrol; Stilbenes; Time Factors; Vasodilation

The polyphenolic compound resveratrol (RSV) has been studied for its protective effects on a variety of conditions, including cardiovascular disease (CVD), reduced exercise capacity, and bone disease. Individuals with chronic kidney disease suffer from a variety of these comorbid conditions, but the efficacy of RSV supplementation in this population is unknown. The objective of this study was to determine the efficacy of resveratrol feeding on factors related to CVD, aerobic capacity, and bone health in a mouse model of uremia. At 8 weeks of age, 28 female apolipoprotein E⁻/⁻ mice underwent a two-step surgical procedure to induce uremia and were randomized to one of the two treatment groups for 16 weeks: 0.04% w/w resveratrol supplemented diet (group designated as RSV) (n=12) or control diet (group designated as CON) (n=16). Cardiovascular risk was determined by analysis of aortic atherosclerotic lesion area and aortic calcium, aerobic capacity was measured by maximal oxygen consumption/maximal aerobic capacity (VO(₂max)) testing, and bone microarchitecture was assessed by microcomputed tomography. RSV animals had significantly fewer aortic atherosclerotic lesions at the site of the ascending aorta and lower aortic calcium at the branch of the coronary arteries compared with CON. Furthermore, there was a significant decline in VO(₂max) from baseline to final testing in the CON group, but VO(₂max) was preserved in the RSV group. Last, RSV had no significant effect on bone architecture. These data indicate that RSV supplementation improves vascular health and preserves aerobic capacity in a model of uremia, suggesting RSV supplementation could be examined as a therapeutic strategy for a critically ill population.

Topics: Animals; Aorta; Calcinosis; Coronary Artery Disease; Dietary Supplements; Disease Models, Animal; Female; Humans; Mice; Oxygen; Resveratrol; Stilbenes; Uremia

Topics: Adiponectin; Anti-Inflammatory Agents; Coronary Artery Disease; Female; Humans; Leukocytes, Mononuclear; Male; Resveratrol; Stilbenes; Transcription Factors; Vitis

Resveratrol has been purported to modify risk factors for obesity and cardiovascular disease. We sought to examine the effects of resveratrol in a porcine model of metabolic syndrome and chronic myocardial ischemia. Yorkshire swine were fed either a normal diet (control), a high cholesterol diet (HCD), or a high cholesterol diet with supplemental resveratrol (HCD-R; 100mg/kg/day) for 11 weeks. After 4 weeks of diet modification a baseline cardiovascular MRI was performed and an ameroid constrictor was placed on the left circumflex coronary artery of each animal to induce chronic myocardial ischemia. At 7 weeks, a second cardiovascular MRI was performed and swine were sacrificed and myocardial tissue harvested. Resveratrol supplementation resulted in lower body mass indices, serum cholesterol, and C-reactive protein levels, improved glucose tolerance and endothelial function, and favorably augmented signaling pathways associated with myocardial metabolism. Interestingly, serum tumor necrosis factor-α levels were not influenced by resveratrol treatment. Immunoblotting for markers of metabolism demonstrated that insulin receptor substrate-1, glucose transporters 1 and 4, and phospho-AMPK were increased in the HCD-R group. Peroxisome proliferator-activated receptor γ and retinol binding protein 4 were downregulated in the HCD-R group as compared to the HCD group. Myocardial perfusion and function at rest as assessed with magnetic resonance imaging were not different between groups. By favorably influencing risk factors, resveratrol may decrease the burden of chronic metabolic disease and improve cardiovascular health.

Topics: Animals; Biomarkers; Cholesterol; Coronary Artery Disease; Diet; Dietary Supplements; Fatty Acids, Nonesterified; Gene Expression Regulation; Glucose Tolerance Test; Glucose Transporter Type 4; Heart; Inflammation; Insulin; Magnetic Resonance Imaging; Metabolic Syndrome; Microvessels; Muscle Cells; Myocardial Ischemia; Oxidation-Reduction; Protein Transport; Resveratrol; Risk Factors; Stilbenes; Swine

Silencing information regulator (SirT1), a NAD-dependent histone deacetylase, is an essential mediator of longevity in normal cells by calorie restriction. SirT1 has many biological functions, including transcription regulation, cell differentiation inhibition, cell cycle regulation, and anti-apoptosis. Resveratrol (RV)-induced SirT1 activation also improves endothelial dysfunction and suppresses vascular inflammation. In this study, we investigated the roles of RV-induced SirT1 activation in endothelial cells under oxidative stress.. SirT1 mRNA expression levels were examined in the endothelium layer (endothelial cells) of cardiac coronary vessels from patients receiving coronary artery bypass graft surgery (CABG) surgery and aged rats using reverse transcriptase polymerase chain reaction (RT-PCR). To further explore the effect of SirT1 activation on oxidative stress-induced aging, senescence-associated β-galactosidase (SA-β-gal) expression in RV-treated human umbilical vein endothelial cells (HUVECs) with or without H(2)O(2) treatment was evaluated.. SirT1 expression was decreased in aged and atherosclerotic vessels in vivo, and significantly reduced in endothelial cells purified from vessel tissues. Furthermore, SirT1 levels were dose-dependently increased in RV-treated HUVECs. The SA-β gal assay showed that RV inhibited the senescent phenotype of H(2)O(2)-treated HUVECs. Reactive oxygen species (ROS) production and the percentage of cells positive for SA-β gal were significantly increased in siRNA-SirT1 (knockdown of SirT1 expression)-treated HUVEC cells. Importantly, the treatment effect of RV was significantly abolished in the oxidative effects of H(2)O(2)-treated HUVECs by siRNA-SirT1.. Our data suggested that SirT1 could be a crucial factor involved in the endothelial cells of atherosclerotic CAGB patients and aging rats. RV is a potential candidate for preventing oxidative stress-induced aging in endothelial cells. RV may also prevent ROS-induced damage via increased endothelial SirT1 expression.

Topics: Animals; Antioxidants; Base Sequence; Cells, Cultured; Cellular Senescence; Coronary Artery Disease; DNA Primers; Endothelial Cells; Gene Knockdown Techniques; Humans; Hydrogen Peroxide; Oxidative Stress; Rats; Resveratrol; RNA, Messenger; RNA, Small Interfering; Sirtuin 1; Stilbenes

Topics: Azithromycin; Chlamydophila Infections; Chlamydophila pneumoniae; Coronary Artery Disease; Female; France; Humans; Male; Microbial Sensitivity Tests; Platelet Aggregation Inhibitors; Primary Prevention; Prognosis; Resveratrol; Risk Assessment; Stilbenes; United States; Wine