Cardiac ischemic preconditioning prevents dystrophin proteolysis by MMP-2 inhibition

Abstract

Dystrophin is a membrane-associated protein responsible for structural stability of the sarcolemma in cardiac myocytes and is very sensitive to ischemic damage. The goal of our study was to determine if ischemic preconditioning could prevent dystrophin breakdown through inhibition of matrix metalloproteinase-2 (MMP-2) activity. Isolated rabbit hearts were subjected to global ischemia with or without reperfusion in order to evaluate if dystrophin is preserved by ischemic preconditioning through MMP-2 inhibition. Ischemic preconditioning significantly reduced the infarct size induced by 30 min of ischemia and 180 min of reperfusion. Importantly, it also diminished dystrophin proteolysis and attenuated MMP-2 activity after 30 min ischemia. Thus, our study shows a novel protective role of ischemic preconditioning as a mechanism of preservation of plasma membrane integrity by inhibiting MMP-2 activation.