Resveratrol increases vascular oxidative stress resistance

Departments of 1 Physiology and 2 Biochemistry, New York Medical College, Valhalla, New York; and 3 The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center, San Antonio, Texas Submitted 17 November 2006 ; accepted in final form 27 December 2006 Epidemiological studies suggest that Mediterranean diets rich in resveratrol are associated with reduced risk of coronary artery disease. 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. We found that oxidized LDL and TNF- elicited significant increases in caspase-3/7 activity in endothelial cells and cultured rat aortas, which were prevented by resveratrol pretreatment (10 –6 –10 –4 mol/l). The protective effect of resveratrol was attenuated by inhibition of glutathione peroxidase and heme oxygenase-1, suggesting a role for antioxidant systems in the antiapoptotic action of resveratrol. Indeed, resveratrol treatment protected cultured aortic segments and/or endothelial cells against increases in intracellular H 2 O 2 levels and H 2 O 2 -mediated apoptotic cell death induced by oxidative stressors (exogenous H 2 O 2 , paraquat, and UV light). Resveratrol treatment also attenuated UV-induced DNA damage (comet assay). Resveratrol treatment upregulated the expression of glutathione peroxidase, catalase, and heme oxygenase-1 in cultured arteries, whereas it had no significant effect on the expression of SOD isoforms. Resveratrol also effectively scavenged H 2 O 2 in vitro. Thus resveratrol seems to increase vascular oxidative stress resistance by scavenging H 2 O 2 and preventing oxidative stress-induced endothelial cell death. We propose that the antioxidant and antiapoptotic effects of resveratrol, together with its previously described anti-inflammatory actions, are responsible, at least in part, for its cardioprotective effects. endothelial cell; comet assay; caloric restriction mimetics; apoptosis; polyphenol; heme oxygenase antioxidant Address for reprint requests and other correspondence: Z. Ungvari or A. Csiszar, Dept. of Physiology, New York Medical College, Valhalla, NY 10595 (e-mail: zoltan_ungvari{at}nymc.edu )