Oestrogen modulates cardiac ischaemic remodelling through oestrogen receptor-specific mechanisms

被引:36
作者
Babiker, F. A.
Lips, D. J.
Delvaux, E.
Zandberg, P.
Janssen, B. J. A.
Prinzen, F.
van Eys, G.
Grohe, C.
Doevendans, P. A.
机构
[1] Univ Hosp Maastricht, Dept Cardiol, Cardiovasc Res Inst, Maastricht, Netherlands
[2] Organon NV, Dept Pharmacol, Oss, Netherlands
[3] Maastricht Univ, Dept Pharmacol & Toxicol, Maastricht, Netherlands
[4] Maastricht Univ, Dept Physiol, Maastricht, Netherlands
[5] Maastricht Univ, Dept Mol Genet, Inst Cardiovasc Res, Maastricht, Netherlands
[6] Med Univ Poliklin, Bonn, Germany
[7] Interuniv Cardiol, Inst Netherlands, Utrecht, Netherlands
[8] Heart Lung Ctr Utrecht, Dept Cardiol, Utrecht, Netherlands
关键词
gender; hormones; myocardial infarction;
D O I
10.1111/j.1748-1716.2006.01633.x
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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)alpha and -beta in this process, using ER alpha- and ER beta-deficient mice. Methods: Wild type (WT) (ER alpha(+/+) and ER beta(+/+)), ER alpha-deficient (ER alpha(-/-)) and ER beta-deficient (ER beta(-/-)) 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 (ER alpha(+/+) and ER beta(+/+)) mice. Surprisingly, E2 treatment did result in smaller infarct sizes in ER alpha(-/-) mice, but increased the infarct size in ER beta(-/-) mice. Increase of the left ventricular mass post-MI was significantly larger in the E2-treated ER alpha(-/-) animals compared with placebo-treated animals. E2 treatment also significantly increased post-MI mortality in ER alpha(+/+), ER beta(+/+) and ER alpha(-/-) animals, but not in ER beta(-/-) mice. Conclusions: Although E2 modulates the infarct size in ER alpha(-/-), it also appears to be responsible for the higher mortality following MI. ER beta appears to be the receptor involved in the modulating effects of E2 in the infarcted heart.
引用
收藏
页码:23 / 31
页数:9
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