Estrogens and atherosclerosis: recent data and future

Clinical and experimental data underscore the cardioprotective effects of e strogens but the mechanisms involved have not yet been characterized. Estro gen replacement therapy improves serum lipoprotein profiles in postmenopaus al women, although this accounts for less than half of the protective effec t. The vascular wall thus appears to constitute the main target of the horm one. This review addresses the potential molecular and cellular mechanisms concerned. Estrogens are active in the three cell populations constituting the vascular wall: endothelial and smooth muscle cells, lymphocytes and mon cytes/macrophages. Functionally competent estrogen receptors, especially th e recently cloned estrogen receptor beta, have been identified in all three categories. Activities of paracrine factors including cytokines and vasoac tive factors, mainly nitric oxide, are induced by estrogen treatment in the undisturbed vascular wall. Estrogens can also modify expression of these f actors induced by the different types of stress that the vascular wall unde rgoes either physiologically (shear stress) or pathologically (atherosclero sis, balloon angioplasty). Finally the respective roles, in the constitutio n of the fatty streak itself of the increased biological activity of nitric oxide and of the modified biology of macrophages under estrogen treatment are discussed.