Mild Therapeutic Hypothermia Alleviated Myocardial Ischemia/Reperfusion Injury via Targeting SLC25A10 to Suppress Mitochondrial Apoptosis

• DOI: 10.1007/s12265-024-10503-z
• Publication Date: 2024-04-03T14:03:07Z
• Authors: Senlin Ma; Yun Song; Yanxin Xu; Chao Wang; Yifan Yang; Yanchao Zheng; Qiuxin Lu; Qingjiang Chen; Jian Wu; Bin Wang; Mingquan Chen
• Keywords: Male; 0301 basic medicine; Myocardial Infarction; Myocardial Reperfusion Injury; Apoptosis; Mitochondria, Heart; Rats; Rats, Sprague-Dawley; Disease Models, Animal; 03 medical and health sciences; Hypothermia, Induced; Animals; Original Article; Myocytes, Cardiac; Apoptosis Regulatory Proteins; Cells, Cultured; Signal Transduction

AbstractMyocardial 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. In ischemia/reperfusion (I/R) rats, MTH treatment significantly improved myocardial injury, attenuated myocardial infarction, and inhibited the mitochondrial apoptosis pathway. The results of proteomics identified SLC25A10 as the main target of MTH treatment. Consistently, SLC25A10 expressions in I/R rat myocardium and hypoxia and reoxygenation (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 mitochondrial apoptosis pathway, which were partially reversed by SLC25A10 deletion. 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. Graphical Abstract