Towards a molecular understanding of the atheropotective effects of estrogens: a review of estrogen effects on endothelial activation

Early phases of atherosclerosis are characterized by an increased adhesion of leukocytes to vascular endothelium, leading to a recruitment of white blood cells into the intima. Leukocyte adhesion is mediated by the expression of specific adhesion molecules on endothelial cells, dependent on a dysfunctional status of vascular endothelium (endothelial activation), potentially caused by the exposure to diverse atherogenic stimuli. Female sex steroid hormones regulate vascular function acting directly on vascular cells, and producing a net anti-inflammatory effect. Among the various mechanisms mediating the anti-atherogenic effects of estrogens, the inhibition of endothelial activation process and of leukocyte adhesion molecule expression are particularly important, for the strategic pathophysiological role played by these processes during atherogenesis. This brief review discusses recent discoveries on the molecular mechanisms of estrogens on endothelial activation, as well as pathophysiological and clinical implications of these effects.