Estrogen receptor activation and cardioprotection in ischemia reperfusion injury.

Estrogen receptor activation and cardioprotection in ischemia reperfusion injury.
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DOI:
10.1016/j.tcm.2010.05.001
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发表时间:
2010-04
影响因子:
9.3
通讯作者:
Sun, Junhui
Sun, Junhui
中科院分区:
医学2区
文献类型:
--
作者:
Deschamps, Anne M.;Murphy, Elizabeth;Sun, Junhui

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绝经前女性的心血管疾病发病率比男性低10%。虽然雌激素和雌激素受体(ER)的激活已被发现有助于女性保护,但涉及的复杂机制尚不清楚。除了改变基因转录外,雌激素还可以通过ER介导的非基因组信号通路发挥心脏保护作用。除了两种经典的细胞核ER亚型ERα和ERβ外,还发现G蛋白偶联的ER(GPR 30或GPER)在心肌细胞中表达,并在缺血再灌注(I/R)损伤中发挥急性心脏保护作用。通过使用亚型特异性ER敲除小鼠模型和/或其特异性调节剂,已经探索了参与心脏保护的不同ER的机制。在这篇综述中,我们将重点关注的信号通路,导致心脏保护I/R损伤后ER激活和讨论的可能性和承诺,具体的ER调节剂治疗缺血性心脏病。
Pre-menopausal females have a comparably lower incidence of cardiovascular disease than their male counterparts. Although estrogen and activation of estrogen receptors (ER) have been found to contribute to female protection, the complex mechanisms involved are unclear. Besides altering gene transcription, estrogen could elicit its cardioprotective effect via ER-mediated nongenomic signaling pathways. In addition to the two classic nuclear ER isoforms, ERα and ERβ, a G-protein coupled ER (GPR30 or GPER), has been found to be expressed in cardiomyocytes and plays an acute cardioprotective role in ischemia reperfusion (I/R) injury. By using isoform-specific ER knockout mouse models and/or their specific modulators, the mechanisms of the different ERs involved in cardioprotection have been explored. In this review, we will focus on the signaling pathways leading to cardioprotection in I/R injury after ER activation and discuss the possibility and promise of specific ER modulators to treat ischemic heart diseases.
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