title: 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.
authors.affiliation: 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.
authors.forename: M A Hassan
authors.initials: MA
authors.lastname: Talukder
authors.forename: Fuchun
authors.initials: F
authors.lastname: Yang
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nishijima
authors.forename: Chun-An
authors.initials: CA
authors.lastname: Chen
authors.forename: Anuradha
authors.initials: A
authors.lastname: Kalyanasundaram
authors.forename: Muthu
authors.initials: M
authors.lastname: Periasamy
authors.forename: Jay L
authors.initials: JL
authors.lastname: Zweier
mesh_terms: 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*
chemical_list: D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases