title: Oestrogen modulates cardiac ischaemic remodelling through oestrogen receptor-specific mechanisms.
abstract: OBJECTIVE
  Observational and clinical studies suggest different responses upon sex hormone replacement therapy in ischaemic heart disease. Few studies, however, have examined the impact of oestrogen receptor-dependent mechanisms on the extent of injury after myocardial infarction (MI). Therefore, we set out to evaluate the effect of oestrogen (E2) replacement on infarct size and remodelling, and the respective role of the oestrogen receptors (ER)alpha and -beta in this process, using ERalpha- and ERbeta-deficient mice.
  
  
  METHODS
  Wild type (WT) (ERalpha(+/+) and ERbeta(+/+)), ERalpha-deficient (ERalpha(-/-)) and ERbeta-deficient (ERbeta(-/-)) mice were ovariectomized and subsequently supplemented with E2 or placebo using subcutaneous 60-day release pellets. MI was induced by left coronary artery ligation. Two weeks following MI, haemodynamic function was assessed and infarct size was determined.
  
  
  RESULTS
  There was no significant difference in infarct size between E2- or placebo-treated WT (ERalpha(+/+) and ERbeta(+/+)) mice. Surprisingly, E2 treatment did result in smaller infarct sizes in ERalpha(-/-) mice, but increased the infarct size in ERbeta(-/-) mice. Increase of the left ventricular mass post-MI was significantly larger in the E2-treated ERalpha(-/-) animals compared with placebo-treated animals. E2 treatment also significantly increased post-MI mortality in ERalpha(+/+), ERbeta(+/+) and ERalpha(-/-) animals, but not in ERbeta(-/-) mice.
  
  
  CONCLUSIONS
  Although E2 modulates the infarct size in ERalpha(-/-), it also appears to be responsible for the higher mortality following MI. ERbeta appears to be the receptor involved in the modulating effects of E2 in the infarcted heart.
authors.affiliation: Department of Cardiology, Cardiovascular Research Institute Maastricht, University Hospital Maastricht, Maastricht, the Netherlands.
authors.forename: F A
authors.initials: FA
authors.lastname: Babiker
authors.forename: D J
authors.initials: DJ
authors.lastname: Lips
authors.forename: E
authors.initials: E
authors.lastname: Delvaux
authors.forename: P
authors.initials: P
authors.lastname: Zandberg
authors.forename: B J A
authors.initials: BJ
authors.lastname: Janssen
authors.forename: F
authors.initials: F
authors.lastname: Prinzen
authors.forename: G
authors.initials: G
authors.lastname: van Eys
authors.forename: C
authors.initials: C
authors.lastname: Grohé
authors.forename: P A
authors.initials: PA
authors.lastname: Doevendans
mesh_terms: D000818:Animals; D001835:Body Weight / Q000502:physiology; D047628:Estrogen Receptor alpha / Q000502:physiology; D047629:Estrogen Receptor beta / Q000502:physiology; D004967:Estrogens / Q000008:administration & dosage / Q000097:blood / Q000502:physiology*; D005260:Female; D006321:Heart / Q000503:physiopathology; D051379:Mice; D009203:Myocardial Infarction / Q000503:physiopathology*; D009929:Organ Size / Q000502:physiology; D010052:Ovariectomy; D011960:Receptors, Estrogen / Q000502:physiology*; D014599:Uterus / Q000503:physiopathology; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D011960:Receptors, Estrogen