Estradiol Accelerates Reendothelialization in Mouse Carotid Artery Through Estrogen Receptor-α but Not Estrogen Receptor-β

Abstract

Background —The atheroprotective effect of 17β-estradiol (E 2 ) has been suggested in women and clearly demonstrated in animals through both an effect on lipid metabolism and a direct effect on the cells of the arterial wall. It has been shown, for example, that E 2 promotes endothelium-dependent relaxation and accelerates reendothelialization in rats. Similar studies have been undertaken in mice to appreciate the molecular mechanism of this process. Methods and Results —We report here a model of electric carotid injury adapted from that described by Carmeliet et al (1997) that allows us to precisely evaluate the reendothelialization process. We demonstrate that E 2 accelerates endothelial regeneration in castrated female wild-type mice. In ovariectomized transgenic mice in which either the estrogen receptor (ER)-α or ERβ gene has been disrupted, E 2 accelerated reendothelialization in female ERβ knockout mice, whereas this effect was abolished in female ERα knockout mice. Conclusions —This study demonstrates that ERα but not ERβ mediates the beneficial effect of E 2 on reendothelialization and potentially the prevention of atherosclerosis.