Increased mortality and aggravation of heart failure in estrogen receptor-beta knockout mice after myocardial infarction.
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 (ERalpha and ERbeta). The present study was undertaken to determine the role of ERbeta in the development of chronic heart failure after experimental myocardial infarction (MI).


RESULTS
Female ERbeta null mice (BERKO(Chapel Hill)) and wild-type littermates (WT) were ovariectomized, given 17beta-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 ERbeta 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 ERbeta and the role of ERalpha in the development of heart failure.
Pelzer
Theo
T
Department of Medicine, University of Würzburg, Würzburg, Germany. pelzer_t@klinik.uni-wuerzburg.de
Loza
Paula-Anahi Arias
PA
Hu
Kai
K
Bayer
Barbara
B
Dienesch
Charlotte
C
Calvillo
Laura
L
Couse
John F
JF
Korach
Kenneth S
KS
Neyses
Ludwig
L
Ertl
Georg
G
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D001835:Body Weight; D004195:Disease Models, Animal; D018450:Disease Progression; D047629:Estrogen Receptor beta / Q000172:deficiency* / Q000235:genetics; D005260:Female; D005838:Genotype; D006333:Heart Failure / Q000209:etiology* / Q000401:mortality* / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000150:complications*; D009206:Myocardium / Q000737:chemistry; D011506:Proteins / Q000032:analysis; D015996:Survival Rate; D020257:Ventricular Remodeling
D047629:Estrogen Receptor beta; D011506:Proteins; D009320:Atrial Natriuretic Factor