Oestrogen modulates cardiac ischaemic remodelling through oestrogen receptor-specific mechanisms
Oestrogen modulates cardiac ischaemic remodelling through oestrogen receptor-specific mechanisms
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DOI：
10.1111/j.1748-1716.2006.01633.x
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发表时间：
2007-01-01
影响因子：
6.3
通讯作者：
Doevendans, P. A.
中科院分区：
文献类型：
--
作者：
Babiker, F. A.;Lips, D. J.;Doevendans, P. A.
目的：观察和临床研究表明缺血性心脏病性激素替代治疗的不同反应。然而，很少有研究探讨雌激素受体依赖性机制对心肌梗死（MI）后损伤程度的影响。因此，我们开始评估雌激素（E2）替代对梗死面积和重塑的影响，以及雌激素受体（ER）α和β在这一过程中的各自作用，使用ER α和ER β缺陷小鼠。方法：野生型（WT）（ER α（+/+）和ER β（+/+）），ER α缺乏（ER α（-/-））和ER β缺陷型将ER β（-/-）小鼠卵巢切除，随后使用皮下60天释放丸补充E2或安慰剂。结扎左冠状动脉诱发心肌梗死。MI后两周，血流动力学功能进行了评估，梗死面积determined.Results：有E2或安慰剂治疗WT（ER α（+/+）和ER β（+/+））小鼠之间的梗死面积没有显着差异。令人惊讶的是，E2治疗确实导致ER α（-/-）小鼠的梗死面积较小，但增加了ER β（-/-）小鼠的梗死面积。与安慰剂治疗的动物相比，E2治疗的ER α（-/-）动物MI后左心室质量的增加显著更大。E2治疗还显著增加ER α（+/+）、ER β（+/+）和ER α（-/-）动物的MI后死亡率，但在ER β（-/-）小鼠中不增加。ER β似乎是参与梗死心脏中E2调节作用的受体。
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.