Levosimendan alleviates myocardial ischemia-reperfusion injury by regulating mitochondrial autophagy through cGAS-STING signaling pathway
Feng Shi, Han Bao, Fanqing Meng, Yunting Pang
Abstract
Levosimendan, a calcium sensitizer, has cardioprotective effects against myocardial ischemia-reperfusion injury (MIRI). Mitophagy plays an important role in MIRI, and the cGAS-STING signaling pathway can participate in mitophagy in a variety of ways. The purpose of this study was to explore the new molecular mechanism by which levosimendan exerts cardioprotective effects in order to provide a new experimental basis for the clinical application of levosimendan. In this study, an isolated MIRI rat model was established, and 48 rats were randomly divided into four groups (n = 12): continuous perfusion group (Group C), ischemia-reperfusion group (IR group), ischemia-reperfusion + levosimendan group (IR + L group), and ischemia-reperfusion + levosimendan + sting activator group (IR + LA group). The hemodynamic indices, myocardial infarction volume, expression of cGAS-STING signaling pathway proteins, and mitophagy-related proteins in isolated rat hearts of the four groups were compared. This study showed that levosimendan can reduce the level of myocardial mitophagy in ischemia-reperfusion rats by inhibiting the cGAS-STING signaling pathway, reducing myocardial injury, and playing a myocardial protective role.