Estrogen receptor beta protects the murine heart against left ventricular hypertrophy.
BACKGROUND
Left ventricular hypertrophy (LVH) displays significant gender-based differences. 17beta-estradiol (E2) plays an important role in this process because it can attenuate pressure overload hypertrophy via 2 distinct estrogen receptors (ERs): ERalpha and ERbeta. However, which ER is critically involved in the modulation of LVH is poorly understood. We therefore used ERalpha-deficient (ERalpha-/-) and ERbeta-deficient (ERbeta-/-) mice to analyze the respective ER-mediated effects.


RESULTS
Respective ER-deficient female mice were ovariectomized and were given E2 or placebo subcutaneously using 60-day release pellets. After 2 weeks, they underwent transverse aortic constriction (TAC) or sham operation. In ERalpha-/- animals, TAC led to a significant increase in ventricular mass compared with sham operation. E2 treatment reduced TAC induced cardiac hypertrophy significantly in wild-type (WT) and ERalpha-/- mice but not in ERbeta-/- mice. Biochemical analysis showed that E2 blocked the increased phosphorylation of p38-mitogen-activated protein kinase observed in TAC-treated ERalpha-/- mice. Moreover, E2 led to an increase of ventricular atrial natriuretic factor expression in WT and ERalpha-/- mice.


CONCLUSIONS
These findings demonstrate that E2, through ERbeta-mediated mechanisms, protects the murine heart against LVH.
Babiker
Fawzi A
FA
Department of Cardiology, Cardiovascular Research Institute Maastricht, University Hospital Maastricht, Netherlands.
Lips
Daniel
D
Meyer
Rainer
R
Delvaux
Els
E
Zandberg
Pieter
P
Janssen
Ben
B
van Eys
Guillaume
G
Grohé
Christian
C
Doevendans
Pieter A
PA
D000818:Animals; D001018:Aortic Diseases / Q000150:complications / Q000201:enzymology / Q000473:pathology; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003251:Constriction, Pathologic / Q000150:complications / Q000201:enzymology / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology*; D047629:Estrogen Receptor beta / Q000502:physiology*; D005260:Female; D006352:Heart Ventricles; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000517:prevention & control*; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D010052:Ovariectomy; D010766:Phosphorylation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D002316:Cardiotonic Agents; D047629:Estrogen Receptor beta; D004958:Estradiol; D009320:Atrial Natriuretic Factor; D048051:p38 Mitogen-Activated Protein Kinases