Effets vasculaires des œstrogènes

Abstract

Hormonal replacement therapy dœs not prevent cardiovacular events in postmenopausal women. In contrast, the incidence of cardiovascular disease is higher in men than in premenopausal women but increases in postmenopausal women, and all animal studies demonstrate a prevention of fatty streak deposit by estradiol. Although estradiol improves the lipoprotein profile, this effect can account for only a minor part of the protective effect. Endothelium appears to be an important target for estradiol, because this hormone potentiates endothelial NO production, thus promoting the beneficial effects of NO as vasorelaxation and inhibition of platelet aggregation. Estradiol accelerates endothelial regrowth, thus favoring vascular healing, and prevents apoptosis of endothelial cells. Estradiol prevents fatty streak deposit through a mechanism which is clearly independent of NO. The immunoinflammatory system appears to play a key role in the development of fatty streak deposit as well as in atherosclerotic plaque rupture. Mice deficient in either in monocyte-macrophage or in lymphocytes are partially protected against fatty streak deposit. Interestingly, the atheroprotective effect of estradiol is absent in mice deficient in T and B lymphocytes. Most of these effects of estradiol are mediated by estrogen receptor α, and are independent of estrogen receptor β. Thus, the inflammatory-immune system appears to be also a major target of estrogens. However, the effects of estrogens on the immuno-inflammatory system appear ambiguous, as in some models, estradiol rather promotes inflammation (by increasing interferon g which could elicit plaque destabilization). A better understanding of the mechanisms of estrogens on the normal and atheromatous arteries is required and should help to optimize the prevention of cardiovascular disease after menopause.