Estrogens and atherosclerosis: recent data and future

Clinical and experimental data underscore the cardioprotective effects of estrogens but the mechanisms involved have not yet been characterized. Estrogen replacement therapy improves serum lipoprotein profiles in postmenopausal women, although this accounts for less than half of the protective effect. The vascular wall thus appears to constitute the main target of the hormone. 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 moncytes/macrophages. Functionally competent estrogen receptors, especially the recently cloned estrogen receptor beta, have been identified in all three categories. Activities of paracrine factors including cytokines and vasoactive factors, mainly nitric oxide, are induced by estrogen treatment in the undisturbed vascular wall. Estrogens can also modify expression of these factors induced by the different types of stress that the vascular wall undergoes either physiologically (shear stress) or pathologically (atherosclerosis, balloon angioplasty). Finally the respective roles, in the constitution 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.