Protective effect of liposomal nanoparticles-loaded with miR-499 antagonist on cardiomyocyte following acute myocardial infarction through suppression of CDC25A

Abstract

Abnormal expression of miR-499 is related to progression of acute myocardial infarction (MI). This study aimed to explore the effect of liposomal nanoparticles carrying miR-499 antagonist on proliferation of cardiomyocytes and myocardial injury, to provide evidence for in-depth analysis of pathogenesis. With 10 sham-operated rats as control group, 10 rats were induced MI. The cardiac function and myocardial tissue morphology were detected. Myocardial cells were transfected with liposomal nanoparticles (blank group), miR-499 agonist (agonist group), liposomal nanoparticles carrying miR-499 agonist (carrier+antagonist group), or CDC25A activator and inhibitor. CDC25A, Akt, and mTOR expressions were determined in the myocardial cells upon treatments, as targeting relationships between miR-499 and CDC25A were detected by dualluciferase reporter gene assay. Myocardial cell proliferation and apoptosis were detected by flow cytometry and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Myocardial infarction (MI) rats exhibited myocardial damage and had irregular cardiac function indexes, and oxidative stress indexes with inflammatory cell infiltration and disordered myocardial architecture. miR-499 antagonist-loaded liposomal nanoparticles significantly elevated the ratio of viable cells, while cell viability was not altered in the other groups (P < 0.05). The miRNA-loaded nanomaterials induced decreased cell apoptosis, and overexpression of miR-499 increased apoptosis (P < 0.05). The expressions of CDC25A, Akt and mTOR proteins were increased by presence of miR-499 antagonist-loaded liposomal nanoparticles. However, silencing of CDC25A induced decreased viability, while the ratio of viable cells was increased in the CDC25A activator group (P < 0.05). There was a direct targeting relationship between miR-499 and CDC25A. It was found that Liposomal nanoparticles carrying miR-499 antagonist down-regulated the expression of CDC25A by down-regulating the expression of miR-499 to activate the Akt/mTOR signaling pathway, and enhanced the cardiomyocyte proliferation following MI.