Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1952-1961
Published online before print October 10, 2002, doi: 10.1161/01.ATV.0000041200.85946.4A
Published online before print October 10, 2002, doi: 10.1161/01.ATV.0000041200.85946.4A
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© 2002 American Heart Association, Inc.
Brief Reviews |
Nonnuclear Actions of Estrogen
From the Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, and Harvard Medical School, Boston, Mass.
Correspondence to James K. Liao, MD, Vascular Medicine Research Unit, Brigham and Women’s Hospital, 65 Landsdowne St, Room 275, Cambridge, MA 02139. E-mail jliao{at}rics.bwh.harvard.edu
Estrogen has long been observed to endow cardiovascular protective effects, as evidenced by sex-specific differences in the incidence of hypertensive and coronary artery disease, the development of atherosclerosis, and myocardial remodeling after infarction. To exert its tissue-specific effects, the classic estrogen receptor (ER) functions as a ligand-dependent transcription factor. However, there is growing evidence that in response to 17ß-estradiol and heterologous signals, the ER can also mediate signaling cascades at the membrane and in the cytoplasm via various second messengers, such as receptor-mediated protein kinases. This review summarizes the current understanding of nonnuclear ER signaling and discusses the relevance to eliciting the beneficial cardiovascular effects of estrogen. These include vasodilation, inhibition of response to vessel injury, limiting myocardial injury after infarction, and attenuating cardiac hypertrophy. Defining the full repertoire of ER function promises to expose novel, highly specific targets for pharmacological interventions and may ultimately lead to the primary and secondary prevention of cardiovascular diseases.
Key Words: estrogen • estrogen receptors • transcription • vasculature • signaling
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