Mild therapeutic hypothermia alleviated myocardial ischemia/reperfusion injury via targeting SLC25A10 to suppress mitochondrial apoptosis

Abstract

Abstract Purpose Myocardial ischemia/reperfusion injury (MI/RI) is identified as a severe vascular emergency and the treatment strategy of MI/RI still needs further improvement. The present study aimed to investigate the potential effects of mild therapeutic hypothermia (MTH) on MI/RI and underlying mechanisms. Methods In in vivoexperiments, rats were subjected to ischemia/reperfusion (I/R) injury with MTH treatment. Cardiac function, myocardial injury, and mitochondrial apoptosis pathway were determined. Total proteins of rat myocardium were obtained for LC-MS/MS analysis. In in vitro experiments, AC16 cardiomyocytes were subjected to hypoxia and reoxygenation (H/R) with MTH treatment. The effects of MTH treatment on myocardial cell injury, mitochondrial dysfunction, mitochondrial apoptosis pathway induced by H/R were analyzed. Results In I/R rats, MTH treatment significantly improved the cardiac function and myocardial injury, and inhibited the activation of mitochondrial apoptosis pathway. Meanwhile, MTH treatment also attenuated myocardial infarction size and alleviated myocardial structural damage induced by I/R. The results of proteomics identified SLC25A10 as the main target of MTH treatment. Consistently, the expressions of SLC25A10 in I/R rat myocardium and H/R cardiomyocytes were significantly suppressed, which was effectively reversed by MTH treatment. In H/R cardiomyocytes, MTH treatment significantly improved cell injury, mitochondrial dysfunction, and inhibited the activation of mitochondrial apoptosis pathway. As expected, SLC25A10 deletion partially abolished the protective effects of MTH treatment on H/R cardiomyocytes. Conclusions These findings suggested that MTH treatment could protect against MI/RI by modulating SLC25A10 expression to suppress mitochondrial apoptosis pathway, providing new theoretical basis for clinical application of MTH treatment for MI/RI.