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Anti-apoptotic Potency of TNFR:Fc Gene in Ischemia/Reperfusion-Induced Myocardial Cell Injury

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Abstract

The aim of the study was to investigate the anti-apoptotic potency of TNFR:Fc gene in ischemia/reperfusion-induced myocardial cell injury and hypoxia/reoxygenation-induced H9c2 rat cardiomyocytes injury. Rats were randomly divided into the following groups (n = 8): (1) sham operation group; (2) ischemia–reperfusion (I/R) rats treated with rAAV-EGFP; (3) I/R rats treated with rAAV-TNFR:Fc group. rAAV-EGFP or rAAV-TNFR:Fc was injected intra-myocardial at four sites on the anterior and posterior walls of left ventricle immediately after the construction of I/R-induced AMI model in rats. The effects of TNFR:Fc on apoptosis and cardiacfunction were observed after 72 h of coronary reperfusion. In the in vitro study, apoptosis was analyzed in H9c2 rat cardiomyocytes treated either with nomoxia alone, or hypoxia/reoxygenation in the presence of rAAV-GFP or rAAV-TNFR:Fc. We found that (1) TNFR:Fc gene improved cardiac function (EF, LVESP, LVEDP and dp/dt max) post I/R-induced AMI; (2) TNFR:Fc gene inhibited I/R-induced apoptosis and attenuated the level of TNF-α in serum and cardiac tissue; (3) TNFR:Fc gene prevented apoptosis in hypoxia/reoxygenation-induced H9c2 rat cardiomyocytes associated with inhibition of caspase-3 activation and normalization of ratio of the Bcl-2/Bax. We concluded that TNFR:Fc gene transfection has anti-apoptotic potency in ischemia/reperfusion-induced myocardial cell injury.

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Acknowledgments

This project was supported by fund from Youth project of National Natural Science Foundation (81100078), the Key Project of Chinese Ministry of Education (211207), Guangzhou Pearl River science and technology new star project plan (2012 J2200063) and Guangdong Science and Technology Department (S2011040001392).

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Authors and Affiliations

  1. Department of Cardiology, the First Affiliated Hospital of Jinan University, Guangzhou, 510630, China

    Jun Guo, Dong Zheng, Hai-Rui Li, Ai-Dong Zhang & Zi-Cheng Li

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  1. Jun Guo
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  2. Dong Zheng
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  3. Hai-Rui Li
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  4. Ai-Dong Zhang
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  5. Zi-Cheng Li
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Correspondence to Jun Guo or Zi-Cheng Li.

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Guo, J., Zheng, D., Li, HR. et al. Anti-apoptotic Potency of TNFR:Fc Gene in Ischemia/Reperfusion-Induced Myocardial Cell Injury. Inflammation 38, 664–671 (2015). https://doi.org/10.1007/s10753-014-9975-1

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  • DOI: https://doi.org/10.1007/s10753-014-9975-1

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