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Current Gene Therapy

Eiditor-in-Chief

ISSN (Print): 1566-5232
ISSN (Online): 1875-5631

Research Article

Cardioprotective Effects of Serca2a Overexpression Against Ischemiareperfusion- induced Injuries in Rats

Author(s): Yan Jiang, Li-Li Tian, Lin-Hui Wang, Xiao-Dong Zhao, Jing-Wei Chen, Koji Murao, Wei Zhu, Liang Dong, Guo-Qing Wang, Wan-Ping Sun and Guo-Xing Zhang*

Volume 17 , Issue 3 , 2017

Page: [248 - 258] Pages: 11

DOI: 10.2174/1566523217666171110175251

Price: $58

Abstract

Aims: The aim of the present study was to assess how genetically increased Sarcoplasmic reticulum Ca2+-ATPase (Serca2a) expression affects cardiac injury after Ischemia/Reperfusion (I/R) exposure and the related mechanisms involved.

Methods and Results: Rats were subjected to Left Anterior Descending coronary artery (LAD) occlusion for 30 min followed by a 24-hour reperfusion. Cardiac function analysis revealed that cardiac function dramatically improved in Serca2a transgenic rats, (Serca2aTG) rats, compared to Wild Type (WT) rats. Serca2aTG rats developed a significantly smaller myocardial infarction size compared to those in WT group. The expression of the Bcl-2 was lower in Serca2aTG rats compared with WT rats; but, Bcl-2 expression was markedly increased in Serca2aTG rats compared with WT after I/R. In addition, Bax was markedly downregulated in Serca2aTG rats compared to WT group after I/R. Meanwhile, autophagy marker LC-3B was increased in Serca2aTG group, and p62 was only increased in WT group but not in Serca2aTG group in response to I/R. Electron microscope observation confirmed that there were more autophagosomes in Serca2aTG group than in WT rats after I/R.

Conclusion: our findings demonstrated that the overexpression of Serca2a plays an important role in myocardial protection from I/R injury and postischemic functional recovery, which may be via antinecrotic, anti-apoptotic and pro-autophagy signal pathways. Our research provides solid basic data and new perspective on clinical treatment in heart failure patients with long-term over-expression of Serca2a.

Keywords: Cardiac protection, Ischemia-reperfusion(I/R), Sarcoplasmic reticulum Ca2+-ATPase (Serca2a), Apoptosis, Autophagy.


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