EFFECT OF NATURAL ESTROGENS ON THE VESSEL WALL - MOLECULAR MECHANISMSAND CLINICAL IMPLICATIONS

Myocardial infarction is the major cause of death in the Western world , Men are more prone to develop coronary artery disease than women, wh o rarely develop coronary disease before menopause. Although epidemiol ogical data has long been available showing a protective effect of est rogen on the vascular system, the underlying mechanisms have been inve stigated more thoroughly only in recent years. Meta-analysis studies h ave revealed that only half of the protective effect on estrogen repla cement therapy is due to its positive effects on the lipid profile and that a large part of this protection is caused by mechanisms distinct from lipid metabolism. It is now known that estrogens also exert effe cts on vascular function and structure of the vessel wall involving nu merous cellular and molecular mechanisms. Here we review actions of na tural estrogens on human vascular cells and arteries. Estrogens can mo dulate vascular function by increasing nitric oxide production via sti mulation of endothelial nitric oxide synthase (eNOS) and decreasing en dothelin-l levels itt vivo. Furthermore, 17 beta-estradiol is an inhib itor of vascular smooth muscle cell proliferation and migration, pheno mena that play a major role in atherosclerotic vascular disease and in the remodelling process. 17 beta-estradiol can also acutely affect va scular tone in human arteries and attenuates constriction induced by c ontractile agonists. Finally, clinical studies have shown that 17 beta -estradiol can acutely and chronically ameliorate vascular function in women with and without vascular disease. In conclusion, results from clinical and in vitro studies confirm the positive effects of natural estrogens on vascular function and protection from coronary heart dise ase. Thus, primary prevention of coronary heart disease by estrogen re placement therapy after the menopause appears to be a new and straight forward approach by which cardiovascular mortality in women can be red uced.