Locally overexpressing hepatocyte growth factor prevents post-ischemic heart failure by inhibition of apoptosis via calcineurin-mediated pathway and angiogenesis
Locally overexpressing hepatocyte growth factor prevents post-ischemic heart failure by inhibition of apoptosis via calcineurin-mediated pathway and angiogenesis
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DOI：
10.1016/j.arcmed.2007.11.001
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发表时间：
2008-02-01
影响因子：
7.7
通讯作者：
Liang, Lirong
中科院分区：
文献类型：
--
作者：
Guo, Yinghua;He, Jianguo;Liang, Lirong
背景心肌梗死是心力衰竭的重要原因。目前，治疗是有限的，新的血运重建方法可能发挥作用。目的：探讨骨髓间充质干细胞（MSCs）表达肝细胞生长因子（HGF）对缺血性心力衰竭的影响。心肌梗死（MI）后4周，将SD道利大鼠随机分为生理盐水对照组、MSC-GFP组、MSC-HGF组、MSC-HGF + CsA组。4周后，检测心室几何结构、心肌功能、血管生成、内皮细胞密度、细胞凋亡以及钙调神经磷酸酶、Akt和Bcl-2蛋白的表达。心肌梗死8周后，MSC-HGF组大鼠左室收缩和舒张功能较其他组明显改善。HGF通过诱导内皮细胞增殖，显著促进血管生成。HGF对细胞凋亡的影响与钙调神经磷酸酶蛋白的表达水平有关。我们的研究结果表明，肝细胞生长因子的过度表达改善缺血心脏功能，通过血管生成和减少凋亡部分介导的钙调磷酸酶的上调。(C)2008年IMSS。爱思唯尔公司出版
Background. Myocardial infarction is a significant cause of heart failure. Currently, therapies are limited and novel revascularization methods may play a role. We investigated the effects of hepatocyte growth factor (HGF) expressed by bone marrow-derived mesenchymal stem cells (MSCs) on post-ischemic heart failure.Methods. Four weeks after myocardial infarction (MI), Sprague Dawley rats were randomly divided into saline control group, MSC-GFP group, MSC-HGF group, and MSC-HGF + CsA group. After another 4 weeks, hearts were analyzed for ventricular geometry, myocardial function, angiogenesis and endothelial cell density, apoptosis and the expression of calcineurin, Akt, and Bcl-2 protein.Results. In MSC-HGF group, rats exhibited better LV systolic and diastolic function compared with other groups after 8 weeks of MI. Angiogenesis was significantly enhanced by HGF through inducing proliferation of endothelial cells. The effects of HGF on apoptosis were associated with the expression level of calcineurin protein.Conclusions. Our findings suggest that overexpression of HGF improved ischemic cardiac function through angiogenesis and reduction of apoptosis partly mediated by upregulation of calcineurin. (C) 2008 IMSS. Published by Elsevier Inc.