Exosomal miRNA-1915-3p, miRNA-4507, and miRNA-3656 serve as clinical diagnostic biomarkers in acute myocardial infarction patients


Authors: Jia Su, Xiaomin Chen

Department of Cardiology, Ningbo No. 1 Hospital, Ningbo, Zhejiang, P.R. China

OBJECTIVES MicroRNA (miRNA) can be used as predictive biomarkers for cardiovascular diseases, especially for acute myocardial infarction (AMI). However, few reports have focused on the value of exosomal miRNAs in the mechanism of the pathophysiological process from stable coronary artery disease (SCAD) to AMI.

METHODS Exosomes were isolated via ExoQuick precipitation after serum samples were collected. The exosomes were then identified by transmission electron microscopy (TEM), Western blotting, and nanoparticle-tracking analysis (NTA). The differential expression of miRNAs in exosomes from 6 AMI and 6 matching SCAD patients was screened using Agilent Human miRNA Microarrays. Target genes of the candidate miRNAs were predicted via an online miRNA database, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Further validation was conducted through quantitative real-time PCR (qRT-PCR) with 60 exosome (30 AMI and 30 SCAD) samples.

RESULTS The expression of 13 miRNAs (miRNA-4507, miRNA-3656, miRNA-6803-5p, miRNA-7108-5p, miRNA-6850-5p, miRNA-4486, miRNA-6741-5p, miRNA-1227-5p, miRNA-3195, miRNA-4634, miRNA-7975, miRNA-6798-3p, and miRNA-1915-3p) was significantly down-regulated in the AMI samples compared with the SCAD samples. In addition, we identified various target genes that are mainly involved in the pathways of cardiac rehabilitation and remodelling, such as the signalling pathways activated downstream by Nerve Growth Factor (NGF) and Fibroblast growth Factor Receptors (FGFRs). Validation of the expression of candidate miRNAs indicated that exosomal miRNA-1915-3p, miRNA-4507, and miRNA-3656 were significantly less expressed in AMI samples than in SCAD samples, and ROC curve (AUC) analysis showed that the expression of these miRNAs resulted in good predictive accuracy [miRNA-1915-3p (AUC 0.772); miRNA-4507 (AUC: 0.684); and miRNA-3656 (AUC: 0.771)], suggesting that serum exosomal miRNA-1915-3p, miRNA-4507, and miRNA-3656 might be predictive for AMI at an early stage. Correlation analysis revealed that the expression of miRNA-1915-3p was negatively correlated with the PLT (r=–0.479, P=0.038), the expression of miRNA-4507 was negatively correlated with LDL-c (r=–0.5, P=0.029), and the expression of miRNA-3656 was related to the LVEF (r=0.471, P=0.042).

CONCLUSIONS Exosomal miRNA-1915-3p, miRNA-4507, and miRNA-3656 might play an important role in the pathophysiology of acute myocardial infarction and could serve as clinical diagnostic biomarkers.

Updated: November 19, 2019 — 2:54 pm