Resveratrol inhibits vascular smooth muscle cell proliferation and induces apoptosis.
OBJECTIVE
In France, despite a high intake of dietary cholesterol and saturated fat, the cardiovascular death rate is one of the lowest among developed countries. This "French paradox" has been postulated to be related to the high red wine intake in France. The aim of this study was to determine the effects of resveratrol, a major polyphenol component of red wine, on vascular smooth muscle cell (SMC) proliferation in vitro.


METHODS
SMCs were exposed to 10(-6) to 10(-4) M resveratrol and cell proliferation was assessed by cell counting. Cell cycle analysis was done by treating cells with propidium iodide followed by flow-activated cell sorting. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling staining.


RESULTS
We demonstrate that resveratrol inhibited bovine aortic SMC proliferation in a dose-dependent manner. The lowest concentration of resveratrol resulting in a significant decrease in SMC proliferation compared with control was 10(-5) M. By flow cytometry, we observed a block in the G1-S phase of the SMC cycle. Resveratrol treatment also resulted in a dose-dependent apoptosis of SMCs but had no effects on SMC morphology.


CONCLUSIONS
The results indicated that vascular SMC proliferation could be inhibited by resveratrol through a block on G1-S phase and by an increase in apoptosis. It supports the conjecture that red wine consumption may have a beneficial effect on cardiovascular mortality.


CONCLUSIONS
Our results suggest that resveratrol inhibits, in a dose-dependent manner, smooth muscle cell proliferation, which may help to partially explain a beneficial effect of wine drinking. This inhibition is related to an early block in the cell cycle and also to a dose-dependent apoptotic effect. The present study demonstrates that resveratrol not only is an indirect marker of a healthy life style and alimentation but may also be directly responsible for the French paradox.
Poussier
Bertrand
B
Department of Vascular Surgery, Yale University School of Medicine, VA Connecticut, New Haven, Connecticut, USA.
Cordova
Alfredo C
AC
Becquemin
Jean-Pierre
JP
Sumpio
Bauer E
BE
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000166:cytology* / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D000975:Antioxidants; D018809:Proliferating Cell Nuclear Antigen; D013267:Stilbenes; D004247:DNA; D000077185:Resveratrol