title: Regulation of endothelial nitric oxide synthase and high-density lipoprotein quality by estradiol in cardiovascular pathology.
abstract: Estrogens have been recognized, in the last 3 decades, as important hormones in direct and indirect modulation of vascular health. In addition to their direct benefit on cardiovascular health, the presence of esterified estrogen in the lipid core of high-density lipoprotein (HDL) particles indirectly contributes to atheroprotection by significantly improving HDL quality and functionality. Estrogens modulate their physiological activity via genomic and nongenomic mechanisms. Genomic mechanisms are thought to be mediated directly by interaction of the hormone receptor complex with the hormone response elements that regulate gene expression. Nongenomic mechanisms are thought to occur via interaction of the estrogen with membrane-bound receptors, which rapidly activate intracellular signaling without binding of the hormone receptor complex to its hormone response elements. Estradiol in particular mediates early and late endothelial nitric oxide synthase (eNOS) activation via interaction with estrogen receptors through both nongenomic and genomic mechanisms. In the vascular system, the primary endogenous source of nitric oxide (NO) generation is eNOS. Nitric oxide primarily influences blood vessel relaxation, the heart rate, and myocyte contractility. The abnormalities in expression and/or functions of eNOS lead to the development of cardiovascular diseases, both in animals and in humans. Although considerable research efforts have been dedicated to understanding the mechanisms of action of estradiol in regulating cardiac eNOS, more research is needed to fully understand the details of such mechanisms. This review focuses on recent findings from animal and human studies on the regulation of eNOS and HDL quality by estradiol in cardiovascular pathology.
authors.affiliation: 1Department of Medicine, University of Patras Medical School, Pharmacology Laboratory, Panepistimioupolis, Rio, Greece.
authors.forename: Kyriakos E
authors.initials: KE
authors.lastname: Kypreos
authors.forename: Sonja
authors.initials: S
authors.lastname: Zafirovic
authors.forename: Peristera-Ioanna
authors.initials: PI
authors.lastname: Petropoulou
authors.forename: Predrag
authors.initials: P
authors.lastname: Bjelogrlic
authors.forename: Ivana
authors.initials: I
authors.lastname: Resanovic
authors.forename: Abdul
authors.initials: A
authors.lastname: Traish
authors.forename: Esma R
authors.initials: ER
authors.lastname: Isenovic
mesh_terms: D000818:Animals; D008076:Cholesterol, HDL / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D009119:Muscle Contraction / Q000502:physiology; D009126:Muscle Relaxation / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis*; D011960:Receptors, Estrogen / Q000378:metabolism*
chemical_list: D008076:Cholesterol, HDL; D011960:Receptors, Estrogen; D009569:Nitric Oxide; D004958:Estradiol; D052250:Nitric Oxide Synthase Type III
keywords: cardiovascular diseases; endothelial nitric oxide synthase; estradiol; estrogen receptor; high-density lipoprotein