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.