Journal: American Journal of Physiology Heart and Circulatory Physiology. 2007. Jan 12 [E-publication ahead of print] Authors and affiliation: Ungvari ZI, Orosz Z, Rivera A, Labinskyy N, Xiangmin Z, Olson SC, Podlutsky A, Csiszar A. Physiology, New York Medical College, Valhalla, New York, USA. PMID: 17220179 Epidemiological studies suggest that Mediterranean diets rich in resveratrol are associated with reduced risk of coronary artery disease. [Resveratrol is obtained for example from grapes/wine, as well as berries such as cranberries and blueberries, and peanuts.] However, the mechanisms by which resveratrol exerts its vasculoprotective effects are not completely understood. Because oxidative stress and endothelial cell injury play a critical role in vascular aging and atherogenesis, we evaluated whether resveratrol inhibits oxidative stress-induced endothelial apoptosis.[Endothelial cells line the entire circulatory system, from the heart to the smallest capillary. Apoptosis is the process of cell death.] We found that oxidized LDL (ox-LDL) and TNFalpha elicited significant increases in caspase 3/7 activity in cultured endothelial cells, which were prevented by resveratrol pre-treatment (10(-6) to 10(-4) mol/). The protective effect of resveratrol was partially reversed by glutathione peroxidase inhibitor mercaptosuccinate, suggesting a role for antioxidant systems in the anti-apoptotic action of resveratrol. Indeed, resveratrol treatment protected cultured aortic segments and/or endothelial cells against increases in intracellular H2O2 levels and H2O2-mediated apoptotic cell death induced by oxidative stressors (exogenous H2O2, paraquat, ultraviolet light). Resveratrol treatment up-regulated the expression of glutathione peroxidase and catalase in cultured arteries, whereas it had no significant effect on expression of SOD isoforms. Resveratrol also effectively scavenged H2O2 in vitro. Thus, resveratrol seems to increase vascular oxidative stress resistance by scavenging H2O2 and preventing oxidative stress-induced endothelial cell death. We propose that the anti-oxidant and anti-apoptotic effects of resveratrol, together with its previously described anti-inflammatory actions, are responsible, at least in part, for its cardioprotective effects. Keywords: oxidative stress, endothelial cell, resveratrol, comet assay, caloric restriction mimetics.