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This Article Full Text Full Text (PDF) All Versions of this Article: 297/5/H1744    most recent 00338.2009v1 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 Google Scholar Articles by Mani, S. K. Articles by Kuppuswamy, D. PubMed PubMed Citation Articles by Mani, S. K. Articles by Kuppuswamy, D.

Calpain inhibition preserves myocardial structure and function following myocardial infarction

¹Division of Cardiology, Department of Medicine, ²Division of Cardiothoracic Surgery, Department of Surgery, and the ³Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, South Carolina

Submitted April 7, 2009 ; accepted in final form September 1, 2009

Cardiac pathology, such as myocardial infarction (MI), activates intracellular proteases that often trigger programmed cell death and contribute to maladaptive changes in myocardial structure and function. To test whether inhibition of calpain, a Ca²⁺-dependent cysteine protease, would prevent these changes, we used a mouse MI model. Calpeptin, an aldehydic inhibitor of calpain, was intravenously administered at 0.5 mg/kg body wt before MI induction and then at the same dose subcutaneously once per day. Both calpeptin-treated (n = 6) and untreated (n = 6) MI mice were used to study changes in myocardial structure and function after 4 days of MI, where end-diastolic volume (EDV) and left ventricular ejection fraction (EF) were measured by echocardiography. Calpain activation and programmed cell death were measured by immunohistochemistry, Western blotting, and TdT-mediated dUTP nick-end labeling (TUNEL). In MI mice, calpeptin treatment resulted in a significant improvement in EF [EF decreased from 67 ± 2% pre-MI to 30 ± 4% with MI only vs. 41 ± 2% with MI + calpeptin] and attenuated the increase in EDV [EDV increased from 42 ± 2 µl pre-MI to 73 ± 4 µl with MI only vs. 55 ± 4 µl with MI + calpeptin]. Furthermore, calpeptin treatment resulted in marked reduction in calpain- and caspase-3-associated changes and TUNEL staining. These studies indicate that calpain contributes to MI-induced alterations in myocardial structure and function and that it could be a potential therapeutic target in treating MI patients.

cardiomyocytes; cell death