Abstract

Background Acute myocardial infarction (AMI) is a leading global cause of death, with extracellular vesicles (EVs) emerging as potential therapeutic mediators. However, the mechanisms by which circulating EVs from different sources influence myocardial injury remain unclear. Method Circulating EVs from AMI patients (AMI-EVs) and healthy controls (N-EVs) were isolated. In vitro assays (CCK8, EdU, flow cytometry, wound healing, angiogenesis) evaluated their effects on cardiomyocyte/endothelial cell proliferation, apoptosis, migration, and tube formation. Immune cell infiltration and immunoglobulin levels in myocardial injury patients were analyzed. Microarray and qPCR identified differentially expressed miRNAs in EVs. CYP1B1, predicted as a target of miR-16-5p via bioinformatics, was validated using dual-luciferase reporter and RNA co-immunoprecipitation. An ischemia-reperfusion (I/R) mouse model assessed EV effects on myocardial injury and PANoptosis. Result N-EVs alleviated I/R-induced myocardial injury in vivo and protected cardiomyocytes/endothelial cells from H2O2-induced damage in vitro. Patients with myocardial injury exhibited IgG deposits, immune cell infiltration, and elevated IgG1/IgG3 levels. N-EVs promoted angiogenesis and cardiomyocyte proliferation while suppressing PANoptosis (combined apoptosis, necroptosis, pyroptosis). Mechanistically, miR-16-5p was enriched in N-EVs and directly targeted CYP1B1, inhibiting its expression and downstream PANoptosis pathways. Conclusion N-EVs mitigate myocardial injury by delivering miR-16-5p to suppress CYP1B1-mediated PANoptosis, highlighting their role in intercellular communication and therapeutic potential for AMI. This study provides insights into EV-based strategies for cardiac repair and fibrosis prevention.