Endothelial progenitor cell-derived microvesicles therapy relieves myocardial infarction symptoms by altering left
Yanling Song1, Shuai Wang2, Huade Mai3
1Department of General Practice, The First Affiliated Hospital of Hainan Medical University 31 Longhua Road, Longhua District, Haikou 570100, Hainan, China.
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.
Insights
Endothelial progenitor cell-derived microvesicles (EPC-MVs) show therapeutic potential for myocardial infarction (MI) by reducing cardiac injury, inflammation, and apoptosis. EPC-MVs remodel the cardiac proteome, offering a promising cell-free therapy for MI.
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Cell Biology
Background:
- Myocardial infarction (MI) remains a leading cause of mortality worldwide.
- Current therapies for MI have limitations in fully restoring cardiac function.
- Endothelial progenitor cells (EPCs) have shown therapeutic benefits, but their clinical application is challenging.
Purpose of the Study:
- To evaluate the therapeutic efficacy of endothelial progenitor cell-derived microvesicles (EPC-MVs) in a rat model of myocardial infarction (MI).
- To investigate the effects of EPC-MVs on cardiac inflammation, apoptosis, and proteomic changes in the left ventricle.
- To explore the underlying molecular mechanisms of EPC-MV therapy.
Main Methods:
- EPCs were isolated and microvesicles (MVs) were derived.
- EPC-MVs were injected into rats with experimentally induced MI.
- Cardiac injury markers, inflammatory cytokines, histology, and apoptosis were assessed.
- Global proteomic analysis of left ventricular tissue was performed, with key targets validated by western blotting.
Main Results:
- EPC-MV treatment significantly reduced cardiac injury, inflammation, and cardiomyocyte apoptosis in MI rats.
- Proteomic analysis revealed significant alterations in inflammatory and metabolic pathways.
- EPC-MVs were shown to inhibit the NLRP3 inflammasome pathway and downregulate downstream inflammatory mediators.
Conclusions:
- EPC-MVs effectively alleviate myocardial ischemic injury by modulating cardiac proteomic profiles.
- EPC-MVs suppress inflammatory and apoptotic signaling pathways post-MI.
- EPC-MVs represent a promising cell-free therapeutic strategy for treating myocardial infarction.
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