Adeno-associated viral vector mediated and cardiac-specific delivery of CD151 gene in ischemic rat hearts
Adeno-associated viral vector mediated and cardiac-specific delivery of CD151 gene in ischemic rat hearts
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DOI：
10.1007/s11596-011-0148-2
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发表时间：
2011-02
期刊：
影响因子：
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通讯作者：
Quan Wei;Zhao-yu Liu;Yu-jie Fei;Danyue Peng;H. Zuo;Xiaolin Huang;Z. Liu;Xin A. Zhang
中科院分区：
文献类型：
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作者：
Quan Wei;Zhao-yu Liu;Yu-jie Fei;Danyue Peng;H. Zuo;Xiaolin Huang;Z. Liu;Xin A. Zhang
我们前期的研究表明，CD 151基因在缺血心脏模型中促进新生血管的形成。为了提高CD 151基因在缺血心肌的靶向性和有效性，我们构建了一种由肌球蛋白轻链（MLC-2 v）启动子调控CD 151基因表达的腺相关病毒（AAV）载体，以实现CD 151基因在缺血心肌的心肌特异性表达，并限制心外器官中不必要的CD 151表达。在大鼠缺血心肌模型中检测该载体的功能。采用免疫印迹法检测缺血心肌区、肝、肾组织中CD 151蛋白的表达，免疫组化法检测缺血心肌区微血管的表达。结果表明，MLC-2 v可显著增强缺血心肌组织中CD 151的表达，而减弱其他器官中CD 151的表达。CD 151的强制表达可以增加缺血心肌中微血管的数量。本研究表明，AAV介导和MLC-2 v调控的CD 151基因在缺血心肌中高度表达，并且心肌梗死后心脏特异性递送更有效地将CD 151靶向缺血心肌。
Our previous studies demonstrated that CD151 gene promoted neovascularization in ischemic heart model. To improve the delivery efficacy and target specificity of CD151 gene to ischemic heart, we generated an adeno-associated virus (AAV) vector in which CD151 expression was controlled by the myosin light chain (MLC-2v) promoter to achieve the cardiac-specific expression of CD151 gene in ischemic myocardium and to limit unwanted CD151 expression in extracardiac organs. The function of this vector was examined in rat ischemic myocardium model. The protein expression of CD151 in the ischemic myocardium areas, liver and kidney was confirmed by using Western blot, while the microvessels within ischemic myocardium areas were detected by using immunohistochemistry. The results showed that MLC-2v significantly enhanced the expression of CD151 in ischemic myocardium, but attenuated its expression in other organs. The forced CD151 expression could increase the number of microvessels in the ischemic myocardium. This study demonstrates the AAV-mediated and MLC-2v regulated CD151 gene is highly expressed in the ischemic myocardium and cardiac-specific delivery that is more efficiently targets CD151 to the ischemia myocardium after myocardial infarction.