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

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.