Hypoxic preconditioning BMSCs-exosomes inhibit cardiomyocyte apoptosis after acute myocardial infarction by upregulating microRNA-24

摘要

OBJECTIVE: To elucidate the regulatory effect of hypoxic preconditioning bone marrow mesenchymal stem cells (BMSCs)-exosomes on cardiomyocyte apoptosis in acute myocardial infarction (AMI) rats. MATERIALS AND METHODS: BMSCs-derived exosomes were extracted by Exoquick method. Expressions of exosome surface markers were determined by Western blot. The AMI model in rats was established by LAD ligation. Rats were randomly assigned into sham group, AMI group, AMI+H-exo group and AMI+N-exo group. MicroRNA-24 expression in rat myocardium was detected at different time points. Subsequently, hypoxic preconditioning or normoxic preconditioning BMSCs-exosomes were intramyocardially injected into rats. Infarct size was calculated through TTC (triphenyltetrazolium chloride) staining. Cardiomyocyte apoptosis was accessed with Terminal Deoxynucleotidyl Transferase dUTP Nick-end Labeling (TUNEL). Heart function of AMI rats was evaluated by echocardiography. Protein expressions of apoptotic genes in rat myocardium were detected by Western blot. RESULTS: The mRNA level of microRNA-24 was higher in H-exo group than N-exo group. Injection of hypoxic preconditioning BMSCs-exosomes markedly upregulated microRNA-24 level, reduced infarct size and improved cardiac function in AMI rats. Protein expressions of Bax, caspase-3 and cleaved-caspase-3 were downregulated by BMSCs-exosomes treatment. H9c2 cells showed upregulated microRNA-24 level and decreased apoptotic rate after incubation with hypoxic preconditioning BMSCs-exosomes. The above cellular performances were partially reversed by transfection of microRNA-24 inhibitor. CONCLUSIONS: Hypoxic preconditioning BMSCs-exosomes inhibit cardiomyocyte apoptosis in AMI rats by upregulating microRNA-24.