Oestradiol inhibition of vascular myointimal proliferation following immune, chemical and mechanical injury.

Abstract

The lower incidence of coronary artery disease in premenopausal women and in postmenopausal women treated with oestrogen supports the hypothesis that oestrogen protects the vasculature from injuries or from responding to injuries with arteriosclerosis. The mechanism remains unknown, although currently the most frequent suggestion is that oestrogen induces beneficial quantitative and qualitative changes in serum lipoprotein concentrations. We studied other mechanisms and in particular the direct effects of 17 beta-oestradiol on vascular smooth muscle and the endothelium. Our focus has been on the vascular response to injury by myointimal and medial thickening, leading to narrowing or occlusion of the vessel. This is frequently seen in coronary arteries within months following angioplasty and a few years following cardiac transplantation. We find that oestradiol treatment protects and reduces the vascular response to injury in three in vivo and one in vitro models: (1) in the rabbit cardiac allograft where oestrogen inhibits accelerated graft atherosclerosis; (2) in monocrotaline- or hypoxia-induced pulmonary hypotension in the rat, where oestrogen attenuates pulmonary artery pressure, right ventricular hypertrophy and medial thickening of the pulmonary artery; (3) oestrogen protects against balloon injury in rabbit aorta; and (4) it inhibits smooth muscle cell proliferation in the porcine left anterior descending coronary artery.