17-BETA-ESTRADIOL INHIBITS APOPTOSIS OF ENDOTHELIAL-CELLS

Endothelial cells provide an antithrombotic and antiinflammatory barri er for the normal vessel wall. Dysfunction of endothelial cells has be en shown to promote atherosclerosis, and normalization of previously d ysfunctional endothelial cells can inhibit the genesis of atheroma. In normal arteries, endothelial cells are remarkably quiescent. Accelera tion of the turnover rate of endothelial cells can lead to their dysfu nction. Apoptosis is a physiological process that contributes to vesse l homeostasis, by eliminating damaged cells from the vessel wall. Howe ver, increased endothelial cell turnover mediated through accelerated apoptosis may alter the function of the endothelium and therefore, pro mote atherosclerosis. Apoptotic endothelial cells can be detected on t he luminal surface of atherosclerotic coronary vessels, but not in nor mal vessels. This finding links endothelial cell apoptosis and the pro cess of atherosclerosis, although a causative role for apoptosis in th is process remains hypothetical. Estrogen metabolites have been shown to be among the most potent anti-atherogenic agents available to date for post-menopausal women. The mechanism of estrogen's protective effe ct is currently incompletely characterized. Here we show that 17 beta- estradiol, a key estrogen metabolite, inhibits apoptosis in cultured e ndothelial cells. Our data support the hypothesis that 17 beta-estradi ol's anti-apoptotic effect may be mediated via improved endothelial ce ll interaction with the substratum, increased tyrosine phosphorylation of pp125 focal adhesion kinase, and a subsequent reduction in program med cell death of endothelial cells. Inhibition of apoptosis by estrog ens may account for some of the anti-atherogenic properties of these c ompounds. (C) 1997 Academic Press.