| Estrogens mediate cardiac hypertrophy in a stimulus-dependent manner. | |
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MedLine Citation:
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PMID: 22759381 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The incidence of cardiac hypertrophy, an established risk factor for heart failure, is generally lower in women compared with men, but this advantage is lost after menopause. Although it is widely believed that estrogens are cardioprotective, there are contradictory reports, including increased cardiac events in postmenopausal women receiving estrogens and enhanced cardiac protection from ischemic injury in female mice without estrogens. We exposed aromatase knockout (ArKO) mice, which produce no estrogens, to both pathologic and physiologic stimuli. This model allows an investigation into the effects of a complete, chronic lack of estrogens in male and female hearts. At baseline, female ArKO mice had normal-sized hearts but decreased cardiac function and paradoxically increased phosphorylation of many progrowth kinases. When challenged with the pathological stimulus, isoproterenol, ArKO females developed 2-fold more hypertrophy than wild-type females. In contrast, exercise-induced physiological hypertrophy was unaffected by the absence of estrogens in either sex, although running performance was blunted in ArKO females. Thus, loss of estrogen signaling in females, but not males, impairs cardiac function and sensitizes the heart to pathological insults through up-regulation of multiple hypertrophic pathways. These findings provide insight into the apparent loss of cardioprotection after menopause and suggest that caution is warranted in the long-term use of aromatase inhibitors in the setting of breast cancer prevention. |
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Authors:
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Christopher D Haines; Pamela A Harvey; Leslie A Leinwand |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-07-03 |
Journal Detail:
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Title: Endocrinology Volume: 153 ISSN: 1945-7170 ISO Abbreviation: Endocrinology Publication Date: 2012 Sep |
Date Detail:
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Created Date: 2012-08-24 Completed Date: 2012-10-29 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: United States |
Other Details:
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Languages: eng Pagination: 4480-90 Citation Subset: AIM; IM |
Affiliation:
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Department of Molecular, Cellular, and Developmental Biology and Biofrontiers Institute, University of Colorado, 3415 Colorado Avenue, Boulder, CO 80309-0347, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Aromatase / genetics, metabolism Blotting, Western Cardiomegaly / genetics, metabolism* Echocardiography Estrogens / metabolism* Female Heart / drug effects Isoproterenol / toxicity Male Mice Mice, Knockout Phosphorylation |
| Grant Support | |
ID/Acronym/Agency:
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HL50560/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Estrogens; 7683-59-2/Isoproterenol; EC 1.14.14.1/Aromatase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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