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腺相关病毒载体介导的CD151基因在缺血大鼠心脏中的心脏特异性递送。

Adeno-associated viral vector mediated and cardiac-specific delivery of CD151 gene in ischemic rat hearts.

作者信息

Wei Quan, Liu Zhaoyu, Fei Yujie, Peng Dan, Zuo Houjuan, Huang Xiaolin, Liu Zhengxiang, Zhang Xin

机构信息

Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

出版信息

J Huazhong Univ Sci Technolog Med Sci. 2011 Feb;31(1):46-51. doi: 10.1007/s11596-011-0148-2. Epub 2011 Feb 19.

Abstract

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.

摘要

我们之前的研究表明,CD151基因在缺血性心脏模型中促进了新血管形成。为了提高CD151基因对缺血性心脏的递送效率和靶向特异性,我们构建了一种腺相关病毒(AAV)载体,其中CD151的表达由肌球蛋白轻链(MLC-2v)启动子控制,以实现CD151基因在缺血心肌中的心脏特异性表达,并限制其在心脏外器官中不必要的表达。在大鼠缺血心肌模型中检测了该载体的功能。通过蛋白质印迹法证实了缺血心肌区域、肝脏和肾脏中CD151的蛋白表达,同时通过免疫组织化学法检测了缺血心肌区域内的微血管。结果表明,MLC-2v显著增强了缺血心肌中CD151的表达,但减弱了其在其他器官中的表达。强制表达CD151可增加缺血心肌中的微血管数量。本研究表明,AAV介导且MLC-2v调控的CD151基因在缺血心肌中高表达,并且在心肌梗死后,心脏特异性递送能更有效地将CD151靶向至缺血心肌。

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