title: Estrogen receptor beta protects the murine heart against left ventricular hypertrophy.
abstract: 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.
authors.affiliation: Department of Cardiology, Cardiovascular Research Institute Maastricht, University Hospital Maastricht, Netherlands.
authors.forename: Fawzi A
authors.initials: FA
authors.lastname: Babiker
authors.forename: Daniel
authors.initials: D
authors.lastname: Lips
authors.forename: Rainer
authors.initials: R
authors.lastname: Meyer
authors.forename: Els
authors.initials: E
authors.lastname: Delvaux
authors.forename: Pieter
authors.initials: P
authors.lastname: Zandberg
authors.forename: Ben
authors.initials: B
authors.lastname: Janssen
authors.forename: Guillaume
authors.initials: G
authors.lastname: van Eys
authors.forename: Christian
authors.initials: C
authors.lastname: Grohé
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Doevendans
mesh_terms: 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
chemical_list: D002316:Cardiotonic Agents; D047629:Estrogen Receptor beta; D004958:Estradiol; D009320:Atrial Natriuretic Factor; D048051:p38 Mitogen-Activated Protein Kinases