title: Estrogen inhibits the vascular injury response in estrogen receptor alpha-deficient mice.
abstract: The atheroprotective effects of estrogen in women are well recognized, but the underlying mechanisms responsible are not well understood. Blood vessel cells express the classic estrogen receptor, ER alpha (ref. 2-6), and are directly affected by estrogen, which inhibits the development of atherosclerotic and injury-induced vascular lesions. We have generated mice in which the ER alpha gene is disrupted and have used a mouse model of carotid arterial injury to compare the effects of estrogen on wild-type and estrogen receptor-deficient mice. Increases in vascular medial area and smooth muscle cell proliferation were quantified following vascular injury in ovariectomized mice treated with vehicle or with physiologic levels of 17 beta-estradiol. Surprisingly, in both wild-type and estrogen receptor-deficient mice, 17 beta-estradiol markedly inhibited to the same degree all measures of vascular injury. These data demonstrate that estrogen inhibits vascular by a novel mechanism that is independent of the classic estrogen receptor, ER alpha.
authors.affiliation: Molecular Cardiology Research Center, New England Medical Center, Tupper Research Institute, Boston, Massachusetts 02111, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Iafrati
authors.forename: R H
authors.initials: RH
authors.lastname: Karas
authors.forename: M
authors.initials: M
authors.lastname: Aronovitz
authors.forename: S
authors.initials: S
authors.lastname: Kim
authors.forename: T R
authors.initials: TR
authors.lastname: Sullivan
authors.forename: D B
authors.initials: DB
authors.lastname: Lubahn
authors.forename: T F
authors.initials: TF
authors.lastname: O'Donnell
authors.forename: K S
authors.initials: KS
authors.lastname: Korach
authors.forename: M E
authors.initials: ME
authors.lastname: Mendelsohn
mesh_terms: D000818:Animals; D002339:Carotid Arteries; D002455:Cell Division; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D011960:Receptors, Estrogen / Q000235:genetics / Q000502:physiology*
chemical_list: D011960:Receptors, Estrogen; D004958:Estradiol