Adeno associated viral vector-delivered and hypoxia response element-regulated CD151 expression in ischemic rat heart  

作　　者：Quan WEI Xiao-lin HUANG Jing-yang LIN Yu-jie FEI Zheng-xiang LIU Xin A ZHANG 

机构地区：[1]Department of Rehabilitation Medicine of Tongl'i Hospital, Tongii Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

出　　处：《Acta Pharmacologica Sinica》2011年第2期201-208,共8页中国药理学报（英文版）

摘　　要：Aim： The aim of this study was to improve the delivery efficacy and target specificity of the pro-angiogenic gene CD151 to the ischemic heart. Methods： To achieve the inducible expression of adeno-associated viral （AAV）-delivered CD151 gene in only the ischemic myocardium, we generated an AAV construct in which CD151 expression can be controlled by the hypoxia response element （HRE） sequence from the human Enolase gene. The function of this vector was examined in rat H9C2 cardiac myoblasts and in ischemic rat myocardium. The expression of CD151 in the areas of ischemic myocardium was confirmed at the mRNA level by real-time PCR and on the protein level by Western blot, whereas the CD151 expression in the microvessels within the areas of ischemic myocardium was detected by immunohistochemistry. Results： HRE significantly enhances the expression of CD151 under hypoxic conditions or in the ischemic myocardium, and forced CD151 expression increases the number of microvessels in the ischemic myocardium. Conclusion： The AAV-mediated, HRE regulated delivery of the CD151 gene shows higher expression in the ischemic myocardium and more efficiently targets CD151 to the hypoxic regions after myocardial infarction.Aim： The aim of this study was to improve the delivery efficacy and target specificity of the pro-angiogenic gene CD151 to the ischemic heart. Methods： To achieve the inducible expression of adeno-associated viral （AAV）-delivered CD151 gene in only the ischemic myocardium, we generated an AAV construct in which CD151 expression can be controlled by the hypoxia response element （HRE） sequence from the human Enolase gene. The function of this vector was examined in rat H9C2 cardiac myoblasts and in ischemic rat myocardium. The expression of CD151 in the areas of ischemic myocardium was confirmed at the mRNA level by real-time PCR and on the protein level by Western blot, whereas the CD151 expression in the microvessels within the areas of ischemic myocardium was detected by immunohistochemistry. Results： HRE significantly enhances the expression of CD151 under hypoxic conditions or in the ischemic myocardium, and forced CD151 expression increases the number of microvessels in the ischemic myocardium. Conclusion： The AAV-mediated, HRE regulated delivery of the CD151 gene shows higher expression in the ischemic myocardium and more efficiently targets CD151 to the hypoxic regions after myocardial infarction.

关 键 词：cardiac ischemia CD151 ANGIOGENESIS gene therapy gene expression hypoxia response element 

分 类 号：R[医药卫生]