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. 2009 Feb;46(2):285-7.
doi: 10.1016/j.yjmcc.2008.10.026. Epub 2008 Nov 12.

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

M A Hassan Talukder  1 , Fuchun Yang, Yoshinori Nishijima, Chun-An Chen, Anuradha Kalyanasundaram, Muthu Periasamy, Jay L Zweier
Affiliations

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

M A Hassan Talukder et al. J Mol Cell Cardiol. 2009 Feb.

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.

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Figures

Fig. 1
Fig. 1
Myocardial infarction and function in hearts subjected to 20-min LAD ligation and 48-hour reperfusion. (A) Immunoblots and bar graphs for SERCA2a protein levels in WT and SERCA2a+/− hearts, calsequestrin as internal control (N = 3/group). (B) Representative sections of hearts stained with phthalo blue and 2,3,5-triphenyltetrazolium chloride after I/R. (C) Percentage of area at risk (AAR) over left ventricle (LV) and infarct area (IA) over AAR. All values are means ± SEM. N =5–6/group; *P<0.05 vs. WT; **P<0.01 vs. WT.
Fig. 2
Fig. 2
Myocardial function and infarction in hearts subjected to 30-min LAD ligation and 48-hour reperfusion. (A) FS (%) before (pre-MI) and after MI (post-MI). (B, C) Please see Fig. 1 for description. N =5–7/group.†P<0.05 vs. Pre-MI; ††P<0.01 vs. Pre-MI; *P<0.05 vs. WT.
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