Review
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World J Cardiol. Jul 26, 2014; 6(7): 638-652
Published online Jul 26, 2014. doi: 10.4330/wjc.v6.i7.638
Calpain system and its involvement in myocardial ischemia and reperfusion injury
Christiane Neuhof, Heinz Neuhof
Christiane Neuhof, Heinz Neuhof, Department of Internal Medicine I, Cardiology, Justus-Liebig-University of Giessen, 35392 Giessen, Germany
Author contributions: All authors contributed equally to this review.
Correspondence to: Christiane Neuhof, MD, Department of Internal Medicine I, Cardiology, Justus-Liebig-University of Giessen, Klinikstrasse 33, 35392 Giessen, Germany. christiane.neuhof@innere.med.uni-giessen.de
Telephone: +49-641-98556690 Fax: +49-641-9919876
Received: December 26, 2013
Revised: January 26, 2014
Accepted: May 29, 2014
Published online: July 26, 2014
Processing time: 237 Days and 1.4 Hours
Abstract

Calpains are ubiquitous non-lysosomal Ca2+-dependent cysteine proteases also present in myocardial cytosol and mitochondria. Numerous experimental studies reveal an essential role of the calpain system in myocardial injury during ischemia, reperfusion and postischemic structural remodelling. The increasing Ca2+-content and Ca2+-overload in myocardial cytosol and mitochondria during ischemia and reperfusion causes an activation of calpains. Upon activation they are able to injure the contractile apparatus and impair the energy production by cleaving structural and functional proteins of myocytes and mitochondria. Besides their causal involvement in acute myocardial dysfunction they are also involved in structural remodelling after myocardial infarction by the generation and release of proapoptotic factors from mitochondria. Calpain inhibition can prevent or attenuate myocardial injury during ischemia, reperfusion, and in later stages of myocardial infarction.

Keywords: Calpain; Calpain inhibition; Calcium overload; Myocardial injury; Ischemia; Reperfusion; Myocardial infarction; Remodelling

Core tip: Calpains, calcium-dependant cytosolic cysteine proteases, are essentially involved in the pathophysiology of myocardial infarction. Their inhibition has shown in animal experiments an enhanced tolerance towards ischemia, a reduction of myocardial infarction and reperfusion injury, and an improvement of the process of remodelling. The availability of specific calpain inhibitors offers new prophylactic and therapeutic possibilities for patients with myocardial infarction, revascularisation and coronary surgery.