Angiogenesis in a rat model following myocardial infarction induced by hypoxic regulation of VEGF(165) gene-transfected EPCs

作者：She, Qiang^*; Xia, Shuang; Deng, Song-Bai; Du, Jian-Lin; Li, Ye-Qing; He, Li; Xiao, Jun; Xiang, Yu-Luan

来源：Molecular Medicine Reports, 2012, 6(6): 1281-1287.

DOI：10.3892/mmr.2012.1112

• angiogenesis
• hypoxia
• gene therapy
• endothelial progenitor cells
• myocardial infarction

Hypoxia-response elements (HREs) regulate the expression of the vascular endothelial growth factor 165 (VEGF(165)) gene and enhance the safety and efficacy of therapeutic angiogenesis. However, the role of hypoxic regulation of VEGF(165) gene-modified stem cells in promoting angiogenesis in the ischemic myocardium remains unclear. In this study, the effects of the hypoxic regulation of genetically modified endothelial progenitor cells (EPCs) on angiogenesis in the ischemic myocardium and on changes in cardiac function following acute myocardial infarction (AMI) were investigated through the transplantation of hypoxia-regulated VEGF(165) gene-modified EPCs into the ischemic myocardium. Rat bone marrow-derived EPCs transfected with plasmid p6HRE-CMV-VEGF(165) (6HRE-VEGF(165)-E), and plasm id pCMV-VEGF(165) (VEGF(165)-E) were injected into rats with a successfully established model of A M I. The levels of VEGF(165) m RNA and protein expression in the EPCs and ischemic myocardium were determined using reverse transcription-polymerase chain reaction and western blot assay, respectively, and the capillary density in the ischemic myocardium and the cardiac function of the rats were detected using immunohistochemistry and echocardiography, respectively. We found that the hypoxia promoter 6HRE-CMV effectively regulated the expression of the VEGF(165) gene in the EPCs and the ischemic myocardium. In rats of the 6HRE-VEGF(165)-E-transplanted group, the levels of VEGF(165) gene expression and capillary density in the ischemic myocardium were significantly higher than those in the other experimental groups. Moreover, cardiac function was also improved compared with that in other groups. VEGF(165) gene-modified EPCs are able to significantly promote angiogenesis in the ischemic myocardium and markedly ameliorate the cardiac function of rats following AMI, especially under 6HRE regulation.

• 出版日期2012-12
• 单位重庆医科大学; 广东省老年医学研究所