Cardiomyocyte-specific Estrogen Receptor Alpha Increases Angiogenesis, Lymphangiogenesis and Reduces Fibrosis in the Female Mouse Heart Post-Myocardial Infarction.
Cardiomyocyte-specific Estrogen Receptor Alpha Increases Angiogenesis, Lymphangiogenesis and Reduces Fibrosis in the Female Mouse Heart Post-Myocardial Infarction.
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DOI：
10.4172/2157-7013.1000153
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发表时间：
2014-01-30
期刊：
影响因子：
--
通讯作者：
Regitz-Zagrosek V
中科院分区：
文献类型：
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作者：
Mahmoodzadeh S;Leber J;Zhang X;Jaisser F;Messaoudi S;Morano I;Furth PA;Dworatzek E;Regitz-Zagrosek V
实验研究表明，17β-雌二醇（E2）和激活的雌激素受体（ER）对缺血性心脏损伤具有保护作用。然而，其潜在的分子机制还不清楚。为了研究心肌细胞中ER α（ERα）在心肌缺血中的作用，我们制备了心肌细胞特异性ERα过表达（ERα-OE）的转基因小鼠，并使它们遭受心肌梗死（MI）。在基础水平，雌性和雄性ERα-OE小鼠显示左心室（LV）质量、LV体积和心肌细胞长度增加。MI后2周，雌性和雄性WT-小鼠以及雄性ERα-OE小鼠的LV体积显著增加，LV壁厚度降低，但雌性ERα-OE小鼠中无此现象。雌激素受体α-OE增强血管生成和淋巴管生成标志物（VEGF，Lyve-1）的表达，并在两种性别的梗死周围区域的新血管形成。而雌激素受体α-OE心肌梗死后纤维化程度减轻，JNK信号通路磷酸化水平升高。总之，我们的研究表明，ERα通过旁分泌方式诱导新生血管形成和受损的纤维化保护雌性小鼠心肌细胞免受缺血后遗症的影响，这两种方式一起可能有助于心脏重塑的减弱。
Experimental studies showed that 17β-estradiol (E2) and activated Estrogen Receptors (ER) protect the heart from ischemic injury. However, the underlying molecular mechanisms are not well understood. To investigate the role of ER-alpha (ERα) in cardiomyocytes in the setting of myocardial ischemia, we generated transgenic mice with cardiomyocyte-specific overexpression of ERα (ERα-OE) and subjected them to Myocardial Infarction (MI). At the basal level, female and male ERα-OE mice showed increased Left Ventricular (LV) mass, LV volume and cardiomyocyte length. Two weeks after MI, LV volume was significantly increased and LV wall thickness decreased in female and male WT-mice and male ERα-OE, but not in female ERα-OE mice. ERα-OE enhanced expression of angiogenesis and lymphangiogenesis markers (Vegf, Lyve-1), and neovascularization in the peri-infarct area in both sexes. However, attenuated level of fibrosis and higher phosphorylation of JNK signaling pathway could be detected only in female ERα-OE after MI. In conclusion, our study indicates that ERα protects female mouse cardiomyocytes from the sequelae of ischemia through induction of neovascularization in a paracrine fashion and impaired fibrosis, which together may contribute to the attenuation of cardiac remodelling.