Calpains are ubiquitous non-lysosomal Ca(2+)-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 Ca(2+)-content and Ca(2+)-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.