Reduced SERCA2a converts sub-lethal myocardial injury to infarction and affects postischemic functional recovery.
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.
Talukder
M A Hassan
MA
Davis Heart and Lung Research Institute, and The Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University College of Medicine and Public Health, Ohio, USA.
Yang
Fuchun
F
Nishijima
Yoshinori
Y
Chen
Chun-An
CA
Kalyanasundaram
Anuradha
A
Periasamy
Muthu
M
Zweier
Jay L
JL
D000818:Animals; D015153:Blotting, Western; D004452:Echocardiography; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000502:physiology*
D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases