Cardiomyopeptide-Regulated PPARγ Expression Plays a Critical Role in Maintaining Mitochondrial Integrity and Preventing Cardiac Ischemia/Reperfusion Injury

Background: Myocardial injury is prone to occur during myocardial ischemia-reperfusion, which further causes adverse cardiac events. Cardiomyopeptide (CMP) has been found to protect the heart against ischemia-reperfusion injury. The present study will explore the molecular and signaling mechanisms associated with the therapeutic effects of CMP. Methods: In this study, the rat myocardial ischemia-reperfusion model was constructed, the pathological changes of myocardial tissues were observed via hematoxylin-eosin (H&E) and Masson staining, and the levels of myocardial injury markers (AST, Mb, TnT) were detected by ELISA. Myocardial tissues of rats in each group were analyzed using transcriptome Sequencing (RNA-seq), and the obtained gene expression profiles were analyzed differentially to determine differentially expressed genes (DEGs). In addition, the signaling pathway related to CMP therapy was found by gene set enrichment analysis (GSEA), and PPARγ was detected by qRT-PCR, WB, and IHC staining. The mitochondrial function of myocardial tissues was detected by mitochondrial respiratory chain activity, JC-1, and Reactive Oxygen Species (ROS). Results: Animal assays showed that CMP could significantly improve myocardial injury and reduce the levels of AST, MB and cTnT. RNA-seq analysis results showed that PPARγ signaling pathway is a potential signaling pathway for CMP treatment of myocardial injury in rats. The experimental results showed that CMP can significantly up-regulate PPARγ expression in myocardial tissues, inhibit ischemia reperfusion-induced myocardial injury, and alleviate mitochondrial respiratory disorders. Conclusion: CMP can improve myocardial injury in rats by alleviating mitochondrial respiratory dysfunction and reducing myocardial tissue damage and inflammatory infiltration via the regulation of PPARγ signaling pathway.

PPARγ; cardiomyopeptide; mitochondrial injury; myocardial ischemia-reperfusion injury.