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This Article Full Text Full Text (PDF) All Versions of this Article: 293/4/H2418    most recent 00663.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Talukder, M. A. H. Articles by Zweier, J. L. Search for Related Content PubMed PubMed Citation Articles by Talukder, M. A. H. Articles by Zweier, J. L.

Expression of SERCA isoform with faster Ca²⁺ transport properties improves postischemic cardiac function and Ca²⁺ handling and decreases myocardial infarction

¹Davis Heart and Lung Research Institute and Division of Cardiovascular Medicine, Department of Internal Medicine, and ²Department of Cell Biology and Physiology, The Ohio State University College of Medicine and Public Health, Columbus, Ohio; and ³Department of Cardiology, Shanghai Changzheng Hospital, Shanghai, China

Submitted 7 June 2007 ; accepted in final form 10 July 2007

Myocardial ischemia-reperfusion (I/R) injury is associated with contractile dysfunction, arrhythmias, and myocyte death. Intracellular Ca²⁺ overload with reduced activity of sarco(endo)plasmic reticulum Ca²⁺-ATPase (SERCA) is a critical mechanism of this injury. Although upregulation of SERCA function is well documented to improve postischemic cardiac function, there are conflicting reports where pharmacological inhibition of SERCA improved postischemic function. SERCA2a is the primary cardiac isoform regulating intracellular Ca²⁺ homeostasis; however, SERCA1a has been shown to substitute SERCA2a with faster Ca²⁺ transport kinetics. Therefore, to further address this issue and to evaluate whether SERCA1a expression could improve postischemic cardiac function and myocardial salvage, in vitro and in vivo myocardial I/R studies were performed on SERCA1a transgenic (SERCA1a^+/+) and nontransgenic (NTG) mice. Langendorff-perfused hearts were subjected to 30 min of global ischemia followed by reperfusion. Baseline preischemic coronary flow and left ventricular developed pressure were significantly greater in SERCA1a^+/+ mice compared with NTG mice. Independent of reperfusion-induced oxidative stress, SERCA1a^+/+ hearts demonstrated greatly improved postischemic (45 min) contractile recovery with less persistent arrhythmias compared with NTG hearts. Morphometry showed better-preserved myocardial structure with less infarction, and electron microscopy demonstrated better-preserved myofibrillar and mitochondrial ultrastructure in SERCA1a^+/+ hearts. Importantly, intraischemic Ca²⁺ levels were significantly lower in SERCA1a^+/+ hearts. The cardioprotective effect of SERCA1a was also observed during in vivo regional I/R with reduced myocardial infarct size after 24 h of reperfusion. Thus SERCA1a^+/+ hearts were markedly protected against I/R injury, suggesting that expression of SERCA 1a isoform reduces postischemic Ca²⁺ overload and thus provides potent myocardial protection.

myocardial ischemia-reperfusion; sarco(endo)plasmic reticulum calcium-adenosine triphosphatase; free radicals; postischemic function

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