MiR-223-3p-loaded Exosomes Derived from Bone Marrow Mesenchymal Stem Cells Ameliorate Mouse Myocardial Infarction Injury through Inhibiting NLRP3 Inflammasome Activation
摘要
Myocardial infarction (MI), a leading cause of morbidity and mortality, necessitates the development of novel therapeutic approaches. The protective effects of mesenchymal stem cell (MSC)-derived exosomes on MI have been well-documented. miR-223-3p has been identified as a regulator of the NOD-like receptor thermal protein domain associated protein 3 (NLPR3), a critical factor in MI. In this study, we explored the therapeutic effects of bone marrow MSC-derived exosomes loaded with miR-223-3p on MI.
MethodsThe MI mouse model was established, followed by the administration of miR-223-3p-loaded exosomes. Cardiac function was evaluated, and ELISA and Western blot assays were employed to assess relevant protein expression. Real-time PCR was used to measure the mRNA expression of target genes.
ResultsBone marrow MSCs were successfully engineered to overexpress miR-223-3p, and exosomes loaded with miR-223-3p were administrated to MI mice. MiR-223-3p directly targeted and inhibited NLRP3 expression in cardiac muscle cells. MI mice treated with exosomes loaded with miR-223-3p exhibited enhanced cardiac function, reduced expression of inflammatory cytokines, and diminished activation of the NLRP3 inflammasome.
ConclusionBone marrow MSC-derived exosomes loaded with miR-223-3p significantly improve MI outcomes by targeting and suppressing NLRP3.