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血管内皮生长因子-A基因电转染促进猪心脏缺血模型中的血管生成。

Vascular endothelial growth factor-A gene electrotransfer promotes angiogenesis in a porcine model of cardiac ischemia.

作者信息

Bulysheva Anna A, Hargrave Barbara, Burcus Nina, Lundberg Cathryn G, Murray Len, Heller Richard

机构信息

Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA.

School of Medical Diagnostics and Translational Sciences, College of Health and Sciences, Old Dominion University, Norfolk, VA.

出版信息

Gene Ther. 2016 Aug;23(8-9):649-656. doi: 10.1038/gt.2016.35. Epub 2016 May 12.

Abstract

This study aimed to assess safety and therapeutic potential of gene electrotransfer (GET) as a method for delivery of plasmid encoding vascular endothelial growth factor A (VEGF-A) to ischemic myocardium in a porcine model. Myocardial ischemia was induced by surgically occluding the left anterior descending coronary artery in swine. GET following plasmid encoding VEGF-A injection was performed at four sites in the ischemic region. Control groups either received injections of the plasmid without electrotransfer or injections of the saline vehicle. Animals were monitored for 7 weeks and the hearts were evaluated for angiogenesis, myocardial infarct size and left ventricular contractility. Arteriograms suggest growth of new arteries as early as 2 weeks after treatment in electrotransfer animals. There is a significant reduction of infarct area and left ventricular contractility is improved in GET-treated group compared with controls. There was no significant difference in mortality of animals treated with GET of plasmid encoding VEGF-A from the control groups. Gene delivery of plasmid encoding VEGF-A to ischemic myocardium in a porcine model can be accomplished safely with potential for myocardial repair and regeneration.

摘要

本研究旨在评估基因电转染(GET)作为一种将编码血管内皮生长因子A(VEGF-A)的质粒递送至猪模型缺血心肌的方法的安全性和治疗潜力。通过手术结扎猪的左前降支冠状动脉诱导心肌缺血。在缺血区域的四个部位进行编码VEGF-A的质粒注射后的GET。对照组要么接受无电转染的质粒注射,要么接受生理盐水载体注射。对动物进行7周的监测,并评估心脏的血管生成、心肌梗死面积和左心室收缩功能。血管造影显示,电转染动物在治疗后2周最早出现新动脉生长。与对照组相比,GET治疗组的梗死面积显著减小,左心室收缩功能得到改善。编码VEGF-A的质粒进行GET治疗的动物死亡率与对照组无显著差异。在猪模型中,将编码VEGF-A的质粒安全地递送至缺血心肌具有心肌修复和再生的潜力。

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