Plasma-derived exosomal miR-183 associates with protein kinase activity and may serve as a novel predictive biomarker of myocardial ischemic injury.

Abstract

Myocardial infarction (MI) is primarily caused by ischemic heart or coronary artery disease and is a major cause of mortality worldwide. Thus, it is necessary to establish reliable biochemical markers for the early diagnosis of MI. MicroRNAs (miRNAs or miR) have been demonstrated to circulate in biological fluids and are enclosed in extracellular vesicles, including exosomes. The current study assessed the differential expression of exosomal miRNAs in the plasma of patients with MI and healthy individuals, and the possible mechanism involved. Plasma-derived exosomes were isolated from patients with MI and healthy control individuals, and vesicles with a membrane were observed using transmission electron microscopy. Furthermore, an exosomal miRNA expression profile was compared between patients with MI and healthy individuals using a miRNA microarray. Significantly differentially expressed miRNAs were validated using reverse transcription-quantitative polymerase chain reaction. To the best of our knowledge, the present study was the first to demonstrate that miR-183 was markedly upregulated in patients with MI compared with healthy individuals. In addition, the relative exosomal miR-183 level increased with the degree of myocardial ischemic injury. Additionally, GO and KEGG analyses demonstrated that miR-183 is primarily involved in cell communication, protein kinase activity regulation and adrenergic signaling in cardiomyocytes. Furthermore, a protein-protein interaction network of all the miR-183 target genes was constructed. The results demonstrated that five core genes (PPP2CB, PPP2CA, PRKCA, PPP2CA, PPP2R5C and PPP2R2A) in the PPI network were also associated with protein kinase activity regulation and adrenergic signaling in cardiomyocytes. Taken together, these data demonstrate that exosomal miR-183 derived from the serum of patients with MI may be a novel diagnostic biomarker involved in the regulation of protein kinase activity. miR-183 may therefore be further developed for clinical use to benefit patients with coronary artery diseases.