TY - JOUR
T1 - Reduced SERCA2a converts sub-lethal myocardial injury to infarction and affects postischemic functional recovery
AU - Talukder, M. A Hassan
AU - Yang, Fuchun
AU - Nishijima, Yoshinori
AU - Chen, Chun An
AU - Kalyanasundaram, Anuradha
AU - Periasamy, Muthu
AU - Zweier, Jay L.
PY - 2009/2
Y1 - 2009/2
N2 - 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.
AB - 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.
KW - Contractile function
KW - Ischemia
KW - Myocardial infarction
KW - Reperfusion
KW - Sarcoplasmic reticulum Ca-ATPase (SERCA)
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UR - http://www.scopus.com/inward/citedby.url?scp=58149349723&partnerID=8YFLogxK
U2 - 10.1016/j.yjmcc.2008.10.026
DO - 10.1016/j.yjmcc.2008.10.026
M3 - Article
C2 - 19046972
AN - SCOPUS:58149349723
SN - 0022-2828
VL - 46
SP - 285
EP - 287
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
IS - 2
ER -