Published online before print March 21, 2005, doi: 10.1161/01.CIR.0000159262.18512.46
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(Circulation. 2005;111:1492-1498.)
© 2005 American Heart Association, Inc.
Heart Failure |
Increased Mortality and Aggravation of Heart Failure in Estrogen Receptor-ß Knockout Mice After Myocardial Infarction
From the Department of Medicine (T.P., P.-A.A.L., K.H., B.B., C.D., G.E.), University of Würzburg, Germany; San Raffaele Hospital (L.C.), University of Milan, Italy; Laboratory of Reproductive and Developmental Toxicology (J.F.C., K.S.K.), Research Triangle Park, NC; and University of Manchester (L.N.), Division of Cardiology, Manchester, United Kingdom.
Correspondence to Theo Pelzer, MD Department of Medicine, University of Würzburg, Josef-Schneider Straße 2, D-97080 Würzburg, Germany. E-mail pelzer_t{at}klinik.uni-wuerzburg.de
Received April 24, 2004; revision received November 20, 2004; accepted November 23, 2004.
Background— Lower mortality rates among women with chronic heart failure than among men may depend in part on the action of female sex hormones, especially estrogens. The biological effects of estrogens are mediated by 2 distinct estrogen receptor (ER) subtypes (ER
and ERß). The present study was undertaken to determine the role of ERß in the development of chronic heart failure after experimental myocardial infarction (MI).
Methods and Results— Female ERß null mice (BERKOChapel Hill) and wild-type littermates (WT) were ovariectomized, given 17ß-estradiol, and subjected to chronic anterior MI (MI; BERKO n=31, WT n=30) or sham operation (sham; BERKO n=14, WT n=14). At 8 weeks after MI, both genotypes revealed left ventricular remodeling and impaired contractile function at similar average infarct size (BERKO-MI 32.9±5% versus WT-MI 33.0±4%); however, BERKO mice showed increased mortality (BERKO-MI 42% versus WT-MI 23%), increased body weight and fluid retention (P<0.01), higher ventricular pro-ANP expression (BERKO-MI 27.9-fold versus sham, WT-MI 5.2-fold versus sham; BERKO-MI versus WT-MI P<0.001), higher atrial natriuretic peptide serum levels, and increased phospholamban expression (P<0.05) compared with WT mice.
Conclusions— Systemic deletion of ERß in female mice increases mortality, aggravates clinical and biochemical markers of heart failure, and contributes to impaired expression of Ca2+-handling proteins in chronic heart failure after MI. Further studies are required to delineate the relative importance of cardiac and vascular effects of ERß and the role of ER in the development of heart failure.
Key Words: receptors • myocardial infarction • heart failure • hormones
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