Document Detail


Estrogens mediate cardiac hypertrophy in a stimulus-dependent manner.
MedLine Citation:
PMID:  22759381     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Christopher D Haines; Pamela A Harvey; Leslie A Leinwand
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-07-03
Journal Detail:
Title:  Endocrinology     Volume:  153     ISSN:  1945-7170     ISO Abbreviation:  Endocrinology     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-08-24     Completed Date:  2012-10-29     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4480-90     Citation Subset:  AIM; IM    
Affiliation:
Department of Molecular, Cellular, and Developmental Biology and Biofrontiers Institute, University of Colorado, 3415 Colorado Avenue, Boulder, CO 80309-0347, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
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:
HL50560/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Estrogens; 7683-59-2/Isoproterenol; EC 1.14.14.1/Aromatase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Heparan Sulfate Proteoglycans Regulate Responses to Oocyte Paracrine Signals in Ovarian Follicle Mor...
Next Document:  Pathway-based classification of cancer subtypes.