Endothelial progenitor cell-derived microvesicles therapy relieves myocardial infarction symptoms by altering left ventricular protein expression.

Objective: To investigate the therapeutic potential of endothelial progenitor cell-derived microvesicles (EPC-MVs) in a rat myocardial infarction (MI) model, focusing on their effects on inflammation, apoptosis, and global proteomic changes in the left ventricle.

Methods: Endothelial progenitor cells (EPCs) were isolated from mouse bone marrow, and microvesicles (MVs) were derived and injected into rats with MI induced by ligation of the left anterior descending artery. Therapeutic efficacy was assessed by measuring inflammatory cytokines (TNF-α, IL-6) and cardiac injury markers (creatine kinase-MB, myoglobin), along with histologic and apoptotic analyses. A global proteomic analysis of left ventricular tissue was performed to explore the underlying molecular mechanisms. Key targets, including components of the NLRP3 inflammasome (NLRP3, Caspase-1, apoptosis-associated speck-like protein containing a CARD), were validated by western blotting.

Results: EPC-MV treatment significantly reduced MI-induced cardiac injury, as evidenced by decreased inflammatory cytokines and cardiac injury markers, preservation of myocardial architecture, reduced fibrosis, and suppression of cardiomyocyte apoptosis. Proteomic analysis revealed significant alterations in inflammatory and metabolic pathways, supported by KEGG and Reactome enrichment analyses. Molecular validation confirmed that EPC-MVs inhibited the activation of the NLRP3 inflammasome and downregulated downstream effectors, including IL-6 and atrial natriuretic peptide.

Conclusion: EPC-MVs alleviated myocardial ischemic injury by remodeling the cardiac proteome, suppressing inflammatory and apoptotic signaling. These results position EPC-MVs as a promising cell-free therapeutic strategy for MI.