Angiogenesis in a rat model following myocardial infarction induced by hypoxic regulation of VEGF165 gene-transfected EPCs

  • Authors:
    • Qiang She
    • Shuang Xia
    • Song-Bai Deng
    • Jian-Lin Du
    • Ye-Qing Li
    • Li He
    • Jun Xiao
    • Yu-Luan Xiang
  • View Affiliations

  • Published online on: September 28, 2012     https://doi.org/10.3892/mmr.2012.1112
  • Pages: 1281-1287
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Abstract

Hypoxia-response elements (HREs) regulate the expression of the vascular endothelial growth factor 165 (VEGF165) gene and enhance the safety and efficacy of therapeutic angiogenesis. However, the role of hypoxic regulation of VEGF165 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 VEGF165 gene-modified EPCs into the ischemic myocardium. Rat bone marrow-derived EPCs transfected with plasmid p6HRE-CMV‑VEGF165 (6HRE-VEGF165-E), and plasmid pCMV-VEGF165 (VEGF165-E) were injected into rats with a successfully established model of AMI. The levels of VEGF165 mRNA 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 VEGF165 gene in the EPCs and the ischemic myocardium. In rats of the 6HRE-VEGF165-E-transplanted group, the levels of VEGF165 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. VEGF165 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.
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December 2012
Volume 6 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
She Q, Xia S, Deng S, Du J, Li Y, He L, Xiao J and Xiang Y: Angiogenesis in a rat model following myocardial infarction induced by hypoxic regulation of VEGF165 gene-transfected EPCs. Mol Med Rep 6: 1281-1287, 2012
APA
She, Q., Xia, S., Deng, S., Du, J., Li, Y., He, L. ... Xiang, Y. (2012). Angiogenesis in a rat model following myocardial infarction induced by hypoxic regulation of VEGF165 gene-transfected EPCs. Molecular Medicine Reports, 6, 1281-1287. https://doi.org/10.3892/mmr.2012.1112
MLA
She, Q., Xia, S., Deng, S., Du, J., Li, Y., He, L., Xiao, J., Xiang, Y."Angiogenesis in a rat model following myocardial infarction induced by hypoxic regulation of VEGF165 gene-transfected EPCs". Molecular Medicine Reports 6.6 (2012): 1281-1287.
Chicago
She, Q., Xia, S., Deng, S., Du, J., Li, Y., He, L., Xiao, J., Xiang, Y."Angiogenesis in a rat model following myocardial infarction induced by hypoxic regulation of VEGF165 gene-transfected EPCs". Molecular Medicine Reports 6, no. 6 (2012): 1281-1287. https://doi.org/10.3892/mmr.2012.1112