Search

Atherosclerotic cardiovascular disease is a leading cause of morbidity and mortality worldwide and revascularization procedures used for treatment often result in restenosis. Resveratrol (RSV), a red wine polyphenol, inhibits low-density lipoprotein-oxidation, suppresses smooth muscle cell (SMC) proliferation, and in more recent studies, enhances the expression of endothelial nitric oxide synthase (eNOS), which can decrease SMC migration, however the majority of these studies were performed in vitro. We hypothesized that RSV may decrease SMC migration and proliferation in vivo, resulting in reduced neointimal growth after carotid artery balloon injury, an established model of restenosis. RSV treatment was given to male Sprague-Dawley rats at a subcutaneous (s.c.) dose of 4mgkg-[sup -1]day[sup -1] for 3 days before arterial injury and was continued after injury. A control group was also studied. Carotid arteries were collected at 4, 14, and 28 days after balloon injury. RSV significantly reduced intimal area by 50% at 28 days (n=8, P<0.01) and decreased intimal SMC proliferation by 45% (BrdU-labeling) at 14 days (n=7, P<0.05) after vessel injury compared to control. Interestingly, RSV also strongly inhibited SMC migration by 77% at 4 days after balloon injury (n=4, P<0.05). This effect was not blocked by co-treatment with the NOS inhibitor N-Nitro-L-arginine methyl ester (L-NAME) (2mgkg[sup -1]day[sup -1]; s.c.) (n=4), indicating an NO-independent effect of RSV. This is the first demonstration of RSV decreasing SMC proliferation and migration in vivo, resulting in an inhibition of neointimal growth. These results support an anti-atherogenic role for RSV and raise the possibility that RSV may have clinical potential in the prevention and treatment of restenosis after angioplasty. [ABSTRACT FROM AUTHOR]