ESTROGEN INHIBITS THE VASCULAR INJURY RESPONSE IN ESTROGEN-RECEPTOR ALPHA-DEFICIENT MICE

The atheroprotective effects of estrogen in women are well recognized( 1), but the underlying mechanisms responsible are not well understood. Blood vessel cells express the classic estrogen receptor, ER alpha (r ef. 2-6), and are directly affected by estrogen, which inhibits the de velopment of atherosclerotic and injury-induced vascular lesions(7,8). We have generated mice in which the ER alpha gene is disrupted(9) and have used a mouse model of carotid arterial injury to compare the eff ects of estrogen on wild-type and estrogen receptor-deficient mice. In creases in vascular medial area and smooth muscle cell proliferation w ere quantified following vascular injury in ovariectomized mice treate d with vehicle or with physiologic levels of 17 beta-estradiol. Supris ingly, in both wild-type and estrogen receptor-deficient mice, 17 beta -estradiol markedly inhibited to the same degree all measures of vascu lar injury. These data demonstrate that estrogen inhibits vascular inj ury by a novel mechanism that is independent of the classic estrogen r eceptor, ER alpha.