MSCs-derived Exosomal miRNA-335-5p Alleviates Apoptosis and Inflammation in Myocardial Infarction by Inhibiting BCL2L11.

BACKGROUND

Myocardial infarction (MI) leads to heart cell death and inflammation, resulting in permanent heart damage. Exosomes derived from mesenchymal stem cells (MSCs), which can deliver miRNAs to cells, have shown potential as therapeutic agents for MI, this study sought to elucidate the role of MSC-derived exosomal miRNA-335-5p in MI.

METHODS

Exosomes secreted from MSCs were observed using transmission electron microscope (TEM) and nanoparticle tracking analysis (NTA). Inflammatory cytokines, cell apoptosis were evaluated. The dual luciferase gene assay was used to validate the interaction between miRNA-335-5p and BCL2-like 11 (BCL2L11). Cardiac function indicators in MI rats were detected using echocardiography. The levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) and cardiac troponin (cTnI) were detected by commercial kits. To confirm fibrosis detection, Masson staining was employed.

RESULTS

MSCs-derived exosomes (MSC-exos) are abundant in miR-335-5p. MSCs-derived exosomal miR-335-5p inhibited hypoxia induced H9c2 cells apoptosis and inflammation, while reducing miRNA-335-5p in MSC-exos does not produce this effect. Mechanically, miRNA-335-5p interacted with BCL2L11 and reduced its expression. Reducing miRNA-335-5p in MSC-exos or overexpressing BCL2L11 can counteract the improvement of MSC-exos on apoptosis and inflammation in H9c2 cells under hypoxic conditions and MI rats.

CONCLUSION

In MI, MSCs-derived exosomal miRNA-335-5p alleviated apoptosis and inflammation by targeting BCL2L11.