Resveratrol increases vascular oxidative stress resistance
Am J Physiol Heart Circ Physiol. 2007 May;292
Ungvari Z, Orosz Z, Rivera A, Labinskyy N, Xiangmin Z, Olson S, Podlutsky A, Csiszar A.
Department of Physiology, New York Medical College, Valhalla, NY 10595, USA. zoltan_ungvari@nymc.edu
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-alpha 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.