Effects of Adenovirus-Mediated Hepatocyte Growth Factor Gene Therapy on Postinfarct Heart Function: Comparison of Single and Repeated Injections.
Effects of Adenovirus-Mediated Hepatocyte Growth Factor Gene Therapy on Postinfarct Heart Function: Comparison of Single and Repeated Injections.
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DOI：
10.1089/hum.2015.119
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发表时间：
2016-08
影响因子：
4.2
通讯作者：
Wei Wang;Mingqing Wang;Hao Wang-;Wei Gao;Zhen Zhang;Sha Zhao;Huijun Xu;Bo Chen;Meixia Zhu;Ze-Zu Wu;Jiangtao Yang;Sheng Wang
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文献类型：
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作者：
Wei Wang;Mingqing Wang;Hao Wang-;Wei Gao;Zhen Zhang;Sha Zhao;Huijun Xu;Bo Chen;Meixia Zhu;Ze-Zu Wu;Jiangtao Yang;Sheng Wang
在慢性缺血性心力衰竭患者中测试单次注射携带人肝细胞生长因子基因（Ad-HGF）的腺病毒的效果的临床试验未能显示心脏功能的一致改善。本研究的目的是评估反复注射Ad-HGF在大鼠梗死后心力衰竭模型中的疗效。采用Sprague道利大鼠心肌梗死后心力衰竭模型，经心包内注射Ad-HGF或Ad-GFP。注射后4周和8周通过磁共振成像监测心脏功能。用免疫印迹法或免疫荧光法检测肝细胞生长因子（HGF）或VIII因子/Ki-67的表达。我们发现，Ad-HGF基因的表达可以延长在体内重复注射和心脏功能显着改善Ad-HGF重复注射组相比，Ad-HGF单次注射组。Ad-HGF重复注射组的新生毛细血管密度同样高于Ad-HGF单次注射组。因此，我们得出结论，分数重复注射的Ad-HGF可能是一个有前途的治疗策略，以改善心脏功能的设置梗死后心力衰竭。
Clinical trials testing the effects of a single injection of adenovirus carrying the human hepatocyte growth factor gene (Ad-HGF) in patients with chronic ischemic heart failure failed to show consistent improvements in cardiac function. The aim of this study was to evaluate the efficacy of repeated injections of Ad-HGF in a rat model of postinfarct heart failure. Ad-HGF or Ad-green fluorescent protein (GFP) was administered to Sprague Dawley rat models of postinfarct heart failure via single or fractional repeated intrapericardial injection. Heart function was monitored by magnetic resonance imaging for 4 and 8 weeks after injections. The expression of HGF or factor VIII/Ki-67 was evaluated by Western blot assay or immunofluorescence. We found that Ad-HGF gene expression could be prolonged in vivo by repeated injections and that cardiac function was significantly improved in the Ad-HGF repeat-injection group compared with the Ad-HGF single-injection group. Newly formed capillary density was similarly higher in the Ad-HGF repeat-injection group compared with that in the Ad-HGF single-injection group. We therefore conclude that fractional repeated injections of Ad-HGF may represent a promising therapeutic strategy to improve cardiac function in the setting of postinfarct heart failure.