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Basic science: Cardiovascular disease basic research
e0143 In vivo study of adenvirus mediated transgenic HIF-1α and its protective effects on cardiac function in experimental myocardial infarction
  1. Li Dongye,
  2. Yan Yan,
  3. Liu Yina,
  4. Liu Chuang,
  5. Zhu Hong,
  6. Pan Defeng,
  7. Zhang Zhuoqi,
  8. Xia Yong
  1. The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China

Abstract

Hypoxia inducible factor-1α (HIF-1α) plays important roles in the regulation of transcriptional responses to hypoxia. In this study, the expression of HIF-1α gene and its downstream gene vascular endothelial growth factor (VEGF) in ischaemic myocardium and the effects of adenovirus mediated transgenic HIF-1α on cardiac function and myocadiocyte apoptosis after acute myocardial infarction (AMI) were investigated. Rabbits performed experimental AMI were divided into four groups randomly and Ad-HIF-1α, Ad-Blank and Rz-HIF-1α were transfected respectively. Sham group was regarded as control. The ultramicrostructure of ischaemic myocardium was observed by electron microscope and light microscope. The mRNA expression of HIF-1α and VEGF was detected by RT-PCR at different time point. The protein expression of HIF-1α, VEGF and CD31was detected by the means of immunohistochemistry and western-blot. The cardiac function of rabbits in each time point were detected by Maclab/8s. Cardiomyocyte apoptosis was detected with TUNEL method at different time point. It was found that the mRNA and protein expression of HIF-1α and VEGF increased at 1d post-infarction, with the peak at 7 d and decreased gradually at 14 and 28 d. At 56 d, HIF-1α mRNA and protein were undetectable, but VEGF mRNA and protein still expressed. The cardiac functional parameter was the highest in Sham group, and the lowest in Rz-HIF-1α group. It was higher in Ad-HIF-1α than in Ad-Blank group. The number of apoptotic cells was the most in Rz-HIF-1α group, and it was less in Ad-HIF-1α than in Ad-Blank group. The number of apoptotic cells decreased with extension of time. There was little apoptotic cells in Sham group. From all above, it was concluded that Ad-HIF-1α could be tranfected and activated effectively. Rz-HIF-1α could suppress the expression of HIF-1α and VEGF. The cardiac function could be improved by Ad-HIF-1α and deteriorated by Rz-HIF-1α. Cardiomyocyte apoptosis could be inhibited by Ad-HIF-1α and increased by Rz-HIF-1α.

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