Myocardial ischemia/reperfusion (I/R) injury is the major limitation for the cardioprotective action of revascularization after myocardial infarction. Lymphocyte adapter protein (Lnk), an adapter protein, has a regulatory role in multiple signaling pathways by functioning as a scaffold for different substrates. However, the involvement of Lnk in myocardial I/R injury remains to be established. In this study, increased expression of Lnk was detected upon the development of myocardial I/R injury. Mice were genetically engineered to investigate the role of Lnk in this pathological process. Upon I/R, myocardial infarction, cardiac dysfunction, inflammation and apoptosis were increased in Lnk-deficient hearts. However, cardiomyocyte-specific overexpression of Lnk protected the hearts against myocardial I/R injury. Mechanistically, we observed that the activation of Akt, but neither ERK1/2 nor STAT3, was influenced by the expression of Lnk upon myocardial I/R injury. Furthermore, the requirement of PI3K-Akt activation for the cardioprotective effect of Lnk was confirmed in rescue experiments using the PI3K inhibitor LY294002. Taken together, our data provide a potential diagnostic and therapeutic strategy for myocardial I/R injury.
Keywords: Akt; Apoptosis; Inflammation; Lnk; Myocardial ischemia/reperfusion injury.
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