title: 17beta-estradiol inhibits apoptosis of endothelial cells.
abstract: Endothelial cells provide an antithrombotic and anti-inflammatory barrier for the normal vessel wall. Dysfunction of endothelial cells has been shown to promote atherosclerosis, and normalization of previously dysfunctional endothelial cells can inhibit the genesis of atheroma. In normal arteries, endothelial cells are remarkably quiescent. Acceleration of the turnover rate of endothelial cells can lead to their dysfunction. Apoptosis is a physiological process that contributes to vessel homeostasis, by eliminating damaged cells from the vessel wall. However, increased endothelial cell turnover mediated through accelerated apoptosis may alter the function of the endothelium and therefore, promote atherosclerosis. Apoptotic endothelial cells can be detected on the luminal surface of atherosclerotic coronary vessels, but not in normal vessels. This finding links endothelial cell apoptosis and the process of atherosclerosis, although a causative role for apoptosis in this process remains hypothetical. Estrogen metabolites have been shown to be among the most potent anti-atherogenic agents available to date for post-menopausal women. The mechanism of estrogen's protective effect is currently incompletely characterized. Here we show that 17beta-estradiol, a key estrogen metabolite, inhibits apoptosis in cultured endothelial cells. Our data support the hypothesis that 17beta-estradiol's anti-apoptotic effect may be mediated via improved endothelial cell interaction with the substratum, increased tyrosine phosphorylation of pp125 focal adhesion kinase, and a subsequent reduction in programmed cell death of endothelial cells. Inhibition of apoptosis by estrogens may account for some of the anti-atherogenic properties of these compounds.
authors.affiliation: Department of Medicine, The Johns Hopkins University, Baltimore, Maryland, 21287, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Alvarez
authors.forename: S J
authors.initials: SJ
authors.lastname: Gips
authors.forename: N
authors.initials: N
authors.lastname: Moldovan
authors.forename: C C
authors.initials: CC
authors.lastname: Wilhide
authors.forename: E E
authors.initials: EE
authors.lastname: Milliken
authors.forename: A T
authors.initials: AT
authors.lastname: Hoang
authors.forename: R H
authors.initials: RH
authors.lastname: Hruban
authors.forename: H S
authors.initials: HS
authors.lastname: Silverman
authors.forename: C V
authors.initials: CV
authors.lastname: Dang
authors.forename: P J
authors.initials: PJ
authors.lastname: Goldschmidt-Clermont
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002417:Cattle; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D003327:Coronary Disease / Q000473:pathology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D008854:Microscopy, Electron; D010766:Phosphorylation; D017698:Postmenopause; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D014443:Tyrosine; D004958:Estradiol; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human