PRAK Plays a Pivotal Role in Protecting the Heart Against Ischemia/ Reperfusion Injury and Myocardial Infarction

p38 regulated/activated protein kinase (PRAK) plays a critical role in modulating cellular survival and biological function. However, the function of PRAK in the regulation of myocardial ischemic injury remains unknown. This study is aimed at determining the function of PRAK in modulating myocardial ischemia/reperfusion injury and myocardial remodeling following myocardial infarction. Hearts were isolated from adult male homozygous PRAK-/- and wild type mice and subjected to global ischemia and reperfusion injury in Langendorff isolated heart perfusion. PRAK-/- mice mitigated post-ischemic ventricular functional recovery and decreased coronary effluent. Moreover, the infarct size in the perfused heart was significantly increased by deletion of PRAK. Western blot showed that deletion of PRAK decreased the phosphorylation of ERK1/2. Furthermore, the effect of deletion of PRAK on myocardialfunction and remodeling was also examined on infarcted mice in which the left anterior descending (LAD) artery was ligated. Echocardiography indicated that PRAK-/- mice had accelerated left ventricular systolic dysfunction, which was associated with increased hypertrophy in the infarcted area. Deletion of PRAK augmented interstitial fibrosis and TUNEL-positive myocytes. Furthermore, immunostaining analysis shows that CD31-postive vascular density and α-SMA capillary staining decreased significantly in PRAK-/- mice. TUNEL analysis demonstrates that deletion of PRAK increased apoptotic myocytes in the infarcted myocardium. These results indicate that deletion of PRAK enhances susceptibility to myocardial ischemia and reperfusion injury, attenuates cardiac performance and angiogenesis, and increases interstitial fibrosis and apoptosis in the infarcted hearts.