Receptor-Dependent and Genomic-Independent Actions of Estrogen in Vascular Protection

Gender differences in cardiovascular mortalityand morbidity exist,(1) and estrogens confer pro-tection against atherosclerotic disease.(2) The female hormone, estrogen (mainly 17β-estradiol), causes a significant lipid-lowering effect; however, this effect can only account for a portion (~1/3) of the athero-protective actions of E2.(3,4) Evidence shows that E2 exerts direct protective effects on blood vessels including an increase in vasodilatation and a reduc-tion in vascular injury response as well as in the development of atherosclerosis.(5) Although the gen-eral functions of estrogen (E2) and the mechanisms through the 'classic ' (genomic) estrogen receptor (ER) to bring about these functions have been exten-sively investigated and reviewed,(6) recent evidence indicates that a receptor-dependent but genomic-independent action of E2 may play a role in the wide-ly observed phenomena of vascular protection offered by E2.(7) The goal of this brief review is thus to summarize the current understanding of this par-ticular mode of E2's action. Estrogen exerts diverse effects on the cardiovas-cular system including systemic effects such as low-ering circulating cholesterol as well as direct vascu-lar effects such as enhancing endothelium-dependent relaxation, and the actions may occur rapidly or only after the prolonged presence of E2.(5,8,9) Currently, two estrogen receptors (ERα and ERβ) are known