Deterioration of Cardiac Function After Acute Myocardial Infarction is Prevented by Transplantation of Modified Endothelial Progenitor Cells Overexpressing Endothelial NO Synthases
Deterioration of Cardiac Function After Acute Myocardial Infarction is Prevented by Transplantation of Modified Endothelial Progenitor Cells Overexpressing Endothelial NO Synthases
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DOI：
10.1159/000343373
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发表时间：
2013-01-01
影响因子：
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通讯作者：
You, Xiaohua
中科院分区：
文献类型：
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作者：
Chen, Xiang;Gu, Mingbiao;You, Xiaohua
背景/目标：在不同的急性和慢性动物模型中，干细胞移植和基因治疗已被证明可以减轻心肌梗死（AMI）后的心肌功能障碍。本研究的目的是评估表达内皮型一氧化氮合酶（eNOS）的内皮祖细胞（EPCs）对梗死心脏的潜在治疗效果。方法：左前降支（LAD）结扎1 h后，注射慢病毒eNOS感染的EPCs。在移植后3天通过ELISA测量心脏组织中的促炎细胞因子TNF-α和IL-1 β水平。于AMI后28天处死动物，用超声心动图和压力-容积系统测定各组大鼠左室功能。心脏组织用苏木精-伊红（H&E）染色和荧光化学分析。用Western blot检测心肌组织中eNOS的表达，用NO测定试剂盒测定心肌组织中NO的产生。结果如下：与培养基对照、eNOS慢病毒载体和正常EPCs相比，在移植慢病毒与eNOS感染的EPCs后3天，心脏组织中的TNF-α和IL-1 β水平显著降低。在AMI后28天，超声心动图和血流动力学测量以及离体心脏研究显示，与培养基对照、eNOS慢病毒载体和正常EPCs相比，在心肌内应用慢病毒eNOS感染的EPCs后，在改善心功能、减小梗死面积和改善梗死周围区域的血管密度方面具有很大的治疗效果。eNOS-EPCs和eNOS慢病毒载体组心肌组织中eNOS表达明显增强，NO水平明显高于假手术组、培养基移植组和EPCs组。结论：EPCs可作为心肌梗死后外源性eNOS表达的载体，通过促进血管生成，有利于防止AMI后心功能的恶化和恢复。版权所有（C）2013 S. Karger AG，巴塞尔
Background/Aims: Stem cell transplantation and gene therapies have been shown to attenuate myocardial dysfunction after myocardial infarction (AMI) in different acute and chronic animal models. The aim of this study was to assess the potential therapeutic efficacy of endothelial NO synthases (eNOS)-expressing endothelial progenitor cells (EPCs) on infarcted hearts. Methods: Lentiviral eNOS-infected EPCs were injected after 1 h of ligation of the left anterior descending artery (LAD). The pro-inflammatory cytokines TNF-alpha and IL-1 beta levels in cardiac tissue were measured by ELISA at 3 days after transplantation. 28 days post AMI (before sacrifice), Left ventricular function of each group was determined by echocardiography and pressure-volume system. Cardiac tissues were analyzed with hematoxylin and eosin (H&E) staining and immunohistochemisty. eNOS expression in cardiac tissues was detected by western blot, and NO production of cardiac tissues was determined using an NO assay kit. Results: TNF-alpha and IL-1 beta levels in cardiac tissue were decreased significantly at 3 days after transplantation of lentiviral with eNOS infected EPCs compared to medium control, eNOS lentiviral vector and normal EPCs. At the 28 day after AMI, echocardiography and hemodynamic measurements, and isolated heart studies showed great therapeutic efficacy in improvement of cardiac function, reduction of infarcted size and improvement of vascular densities in the peri-infarct region after intramyocardial application of lentiviral eNOS-infected EPCs compared to medium control, eNOS lentiviral vector and normal EPCs. The eNOS overexpression in cardiac tissue was observed in the eNOS-EPCs and eNOS lentiviral vector group, and NO levels were increased significantly in the eNOS-EPCs and eNOS lentiviral vector group compared to the other three groups (sham operated group, transplantation of medium or EPCs group). Conclusion: EPCs can be an attractive vehicle for the exogenous eNOS expression into heart after infarction, which is beneficial to prevent deterioration and promote restoration of cardiac function after AMI by improving angiogenesis. Copyright (C) 2013 S. Karger AG, Basel