914-75 The Role of Estradiol 17βon Free Radical Induced Vascular Myointimal Hyperplasia

Abstract

Oxygen free radicals may be involved in vascular hyperplasia by promoting smooth muscle cell proliferation, a response potentiated by endothelial damage. Estradiol 17βprotects against vascular injury in experimental arteriosclerosis and inhibits proliferation of primary cultures of vascular smooth muscle cells. We studied the in vitroeffect of estradiol 17βon vascular smooth muscle cell hyperplasia induced by the superoxide anions (O2-•). Intact and denuded rat aortic segments were incubated overnight at 37° C in 2 ml Eagle's minimal essential medium supplemented with gentamycin and glutamine, without phenol red. The segments were challenged with either vehicle alone or the O2-•generating system (Xanthine and xanthine oxidase) for 4 hrs. We found that O2-•significantly enhanced 3H-thymidine incorporation, an effect potentiated by the absence of the endothelium (Intact vessel 8.3 × 105 ± 0.1 × 105vs denuded vessel 2.5 × 106 ± 1.3 × 105P < 0.01). This effect was inhibited by superoxide dismutase. Estradiol 17β(30 nM) significantly inhibited free radical induced 3H-thymidine uptake in both intact and denuded vessels. We conclude that an intact endothelium may protect against free radical induced smooth muscle cell proliferation. Estradiol 17βmay also protect against free radical induced vascular proliferation by a mechanism independent of the endothelium.