Increased Mortality and Aggravation of Heart Failure in Estrogen Receptor-β Knockout Mice After Myocardial Infarction

Author:

Pelzer Theo1,Loza Paula-Anahi Arias1,Hu Kai1,Bayer Barbara1,Dienesch Charlotte1,Calvillo Laura1,Couse John F.1,Korach Kenneth S.1,Neyses Ludwig1,Ertl Georg1

Affiliation:

1. 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.

Abstract

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 (ERα and ERβ). The present study was undertaken to determine the role of ERβ in the development of chronic heart failure after experimental myocardial infarction (MI). Methods and Results— Female ERβ null mice (BERKO Chapel Hill ) and wild-type littermates (WT) were ovariectomized, given 17β-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 ERβ in female mice increases mortality, aggravates clinical and biochemical markers of heart failure, and contributes to impaired expression of Ca 2+ -handling proteins in chronic heart failure after MI. Further studies are required to delineate the relative importance of cardiac and vascular effects of ERβ and the role of ERα in the development of heart failure.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine

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