Oestrogen modulates cardiac ischaemic remodelling through oestrogen receptor-specific mechanisms

Aim: 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)α and ‐β in this process, using ERα‐ and ERβ‐deficient mice. Methods: Wild type (WT) (ERα^+/+ and ERβ^+/+), ERα‐deficient (ERα^−/−) and ERβ‐deficient (ERβ^−/−) 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 (ERα^+/+ and ERβ^+/+) mice. Surprisingly, E2 treatment did result in smaller infarct sizes in ERα^−/− mice, but increased the infarct size in ERβ^−/− mice. Increase of the left ventricular mass post‐MI was significantly larger in the E2‐treated ERα^−/− animals compared with placebo‐treated animals. E2 treatment also significantly increased post‐MI mortality in ERα^+/+, ERβ^+/+ and ERα^−/− animals, but not in ERβ^−/− mice. Conclusions: Although E2 modulates the infarct size in ERα^−/−, it also appears to be responsible for the higher mortality following MI. ERβ appears to be the receptor involved in the modulating effects of E2 in the infarcted heart.