Resveratrol and Cardiovascular Diseases

Abstract

The increased incidence of cardiovascular diseases (CVDs) has stimulated research for substances that could improve cardiovascular health. Among them, resveratrol (RES), a polyphenolic compound notably present in grapes and red wine, has been involved in the "French paradox". RES is known for its antioxidant and anti-inflammatory properties and for its ability to upregulate endothelial NO synthase (eNOS). RES was able to scavenge (•)OH/O₂(•-) and peroxyl radicals, which can limit the lipid peroxidation processes. Moreover, in bovine aortic endothelial cells (BAEC) under glucose-induced oxidative stress, RES restored the activity of dimethylargininedimethylaminohydrolase (DDAH), an enzyme that degrades an endogenous inhibitor of eNOS named asymmetric dimethylarginine (ADMA). Thus, RES could improve (•)NO availability and decrease the endothelial dysfunction observed in diabetes. Preclinical studies have made it possible to identify molecular targets (SIRT-1, AMPK, Nrf2, NFκB…); however, there are limited human clinical trials, and difficulties in the interpretation of results arise from the use of high-dose RES supplements in research studies, whereas low RES concentrations are present in red wine. The discussions on potential beneficial effects of RES in CVDs (atherosclerosis, hypertension, stroke, myocardial infarction, heart failure) should compare the results of preclinical studies with those of clinical trials.

Keywords: antioxidant; atherosclerosis; clinical; heart failure; hypertension; inflammation; myocardial infarction; preclinical; resveratrol.

Figure 1

Deleterious effects of oxidative stress on ^•NO bioavailability, and potential beneficial action of resveratrol (RES) as an antioxidant and as a modulator of the dimethylaminohydroase (DDAH)/asymmetric dimethylarginine (ADMA) pathway. CVDs could lead to increased ADMA concentrations (due to DDAH inhibition) and activation of NADPH oxidase, leading to oxidative stress. ADMA and peroxynitrite both induce eNOS decoupling, resulting in a decreased ^•NO availability. RES could act as an antioxidant agent (radical scavenging and stimulation of antioxidant defenses) and as an activator of DDAH. ADMA: asymmetric dimethylarginine; DDAH: dimethylarginine dimethylaminohydrolase; eNOS: endothelial NO synthase; PRMT: protein methyltransferase; ROS: Reactive oxygen species; SDMA: symmetric dimethylarginine.

Figure 2

Some of the potential effects of resveratrol (RES) towards atherogenesis and impaired metabolism. AMPK: AMP-activated protein kinase; ARE: antioxidant response element; eNOS: endothelial NO synthase; HMG-CoA reductase: 3-hydroxy-3-methyl-glutaryl-CoA reductase; ICAM-1: intercellular adhesion molecule-1; LDL: low density lipoprotein; MCP-1: monocyte chemotactic protein-1; NF-κB: nuclear factor-kappa B; Nox1: NADPH oxidase 1; Nrf2: nuclear factor (erythroid-derived 2)-like 2; PAI-1: plasminogen activator inhibitor-1; PGC-1αperoxisome proliferator-activated receptor-γ co-activator 1α; ROS: reactive oxygen species; SIRT-1: silent information regulator 2/sirtuin 1; SMC: smooth muscle cells; VCAM-1: vascular cell adhesion molecule-1.