Characterized Expression Of MicroRNAs In Plasma Exosome In Patients With Coronary Chronic Total Occlusion

Backgrounds: Even with similar coronary artery occlusion, chronic total occlusion (CTO) has different clinical features from acute myocardial infarction (AMI). MicroRNAs (miRNA; miR) have been regarded as biomarker to identify heterogenous patients, as well as new therapeutic targets in cardiovascular disease. We aimed to identify exosomal miRNA important for CTO. Methods: Patients with percutaneous coronary intervention (PCI) of CTO (n=30) and AMI (n=30) were performed miRNA expression profiling via exosomal small RNA sequencing in the plasma for these groups. Receiver operating characteristic (ROC) analysis, gene ontology, and functional pathway were analyzed in the miRNA exhibiting >4 absolute fold changes with FDR < 0.05. Results: We detected 10 miRNAs -including miR-21-5p, miR-206, miR-215-5p, and miR-1-3p upregulated in CTO and 3 miRNAs -including miR-9-5p, miR-3529-3p, and miR-127-3p downregulated in CTO as compared to AMI (FDR q < 0.05). Gene enrichment and pathway analysis showed that the target genes of the 10 upregulated miRNAs were involved in regulation of osteoblast proliferation and interleukin-4 and interleukin-13 signaling. In contrast, the target genes of the 3 down-regulated miRNAs were enriched in heart valve development and blood vessel development. We selected 7 miRNAs -including miR-21-5p, miR-206, miR-215-5p, miR-1-3p, miR-9-5p, miR-3529-3p, and miR-127-3p which were related to major pathway term in gene ontology and validated by quantitative real-time polymerase chain reaction (qRT-PCR). In qRT-PCR analysis, the expression levels of miR-9-5p and miR-127-3p of plasma exosome were both lower in CTO than those of AMI, similar to the results of exosomal small RNA sequencing. The ROC curve were analyzed in the 2 miRNAs and for the integrative miRNA expression score showed high accuracy in distinguishing between the CTO and AMI (AUC = 0.948) with 79% specificity and 97% sensitivity. Conclusions: We identified significantly different miRNA expression patterns between the CTO and AMI. The levels of these miRNAs in plasma exosomes may be promising markers that distinguish CTO from AMI.