Reduced SERCA2a converts sub-lethal myocardial injury to infarction and affects postischemic functional recovery

Abstract The goal of the present study was to assess how reduced SERCA2a expression affects in vivo myocardial ischemia/reperfusion (I/R) injury. We specifically wanted to determine to what extent hearts with reduced SERCA2a levels are susceptible to in vivo I/R injury. Therefore, we examined the effects of different ischemic periods on post-ischemic myocardial injury in wild-type (WT) and SERCA2a heterozygous knockout (SERCA2a+/− ) mice expressing lower levels of SERCA2a pump in vivo . Following 20-min ischemia and 48-hour reperfusion, SERCA2a+/− mice developed significant myocardial infarction (MI) compared to negligible infarction in WT mice (14 ± 3% vs. 3 ± 1%, P < 0.01); whereas following 30-min ischemia, the infarction was significantly larger in SERCA2a+/− mice compared to WT mice (49 ± 5% vs. 37 ± 3%, P < 0.05). Further, echocardiographic analysis revealed worsened postischemic contractile function in SERCA2a+/− mice compared to WT mice. Thus, these findings demonstrate that maintaining optimal SERCA2a function is critical for myocardial protection from I/R injury and postischemic functional recovery.