Role of estrogen receptors in the vascular system

Estrogens have been shown to exert significant benefits on the cardiovascular system both in animals and in postmenopausal women. However, the exact mechanism of these effects are, for the most part, still unknown. The goal of this paper is to evaluate the role of estrogen receptors (ER) in mediating some of the cardiovascular beneficial actions of 17beta-estradiol (E2). This analysis was possible because of the availability of ERalpha (ERalphaKO) and ERbeta-deficient (ERbetaKO) mice, and access to a patient with ERalpha-deficiency. Experimental results obtained in our laboratory demonstrated that the ERalpha subtype mediates E2-induced increase in endothelial nitric oxide production and facilitation of fibroblast growth factor-elicited angiogenesis in vivo. Others have confirmed these findings. Experiments using a novel ER-antagonist and ApoExERalpha double-knockout mice proved that ERalpha mediates some of the antiatherosclerotic effects of E2 as well. In contrast, both the ERalpha and ERbeta subtypes appear to mediate the beneficial effects of E2 on vascular smooth muscle proliferation after vessel injury. The young male patient with ERalpha-deficiency exhibited reduced endothelial nitric oxide production and premature coronary arteriosclerosis. These studies in mice and a male human subject suggest that absence of functional ER may represent a novel risk factor for cardiovascular diseases. (C) 2002 Elsevier Science Inc. All rights reserved.