Gender differences in the effect of genistein on vascular smooth muscle cells: A possible cardioprotective effect?

Objective: Isoflavones are a class of phytoestrogens found abundantly in soybeans. They share structural similarity to 17-beta-estradiol, bind to the estrogen receptors alpha and beta, and produce estrogenic or antiestrogenic effects. Atherosclerosis is an inflammatory-mediated fibroproliferative response to injury to the arterial wall. Vascular smooth muscle cells (VSMCs) are the prominent cells in the atherosclerotic plaque. VSMCs contain estrogen receptors and, at physiologic concentrations, 17-beta-estradiol-inhibited proliferation of VSMCs from sexually mature female pigs. We determined if genistein inhibited proliferation and altered matrix protein production in VSMCs from coronary arteries of sexually mature pigs. Methods: The effect of genistein on cell proliferation was assessed by thymidine incorporation. The effect of genistein on matrix protein production in VSMCs was assessed by Western blot analysis. Results and Conclusion: We demonstrate gender-specific effects in the proliferation of coronary artery vascular smooth muscle cells obtained from a sexually mature pig model treated with genistein at physiologically relevant concentrations. There were no differences in the amount of estrogen receptor proteins between the genders, suggesting that nongenomic mechanisms may be responsible for these effects. Genistein also upregulated matrix protein expression, which may be related to the formation of the atherosclerotic plaque. Overall, these results suggest possible cardioprotection by genistein.