MicroRNA Expression Profiles of Epicardial Adipose Tissue-Derived Exosomes in Patients with Coronary Atherosclerosis

Abstract

Background and Aims: Epicardial adipose tissue, exosomes, and miRNAs have important activities in atherosclerosis. The purpose of this study was to establish miRNA expression profiles of epicardial adipose tissue-derived exosomes in patients with coronary atherosclerosis. Methods: Biopsies of epicardial adipose tissue were obtained from patients with and without coronary artery disease (CAD, n = 12 and NCAD, n = 12) during elective open-heart surgeries. Tissue was incubated with DMEM-F12 for 24 hours. Exosomes were isolated, then nanoparticle tracking analysis, transmission electron microscopy, and immunoblotting were performed to confirm the existence of exosomes. Total RNA in exosomes was subjected to high-throughput sequencing to identify differentially expressed miRNAs. MicroRNA target gene prediction was performed, and target genes were analyzed by Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and mirPath to identify function. Reverse transcription quantitative PCR was performed to confirm the differentially expressed miRNAs. Results: Fifty-three unique miRNAs were identified (adjusted p < 0.05, fold of change >2), among which 32 miRNAs were upregulated and 21 miRNAs were downregulated in coronary artery disease patients. Reverse transcription quantitative PCR validated the results for seven miRNAs including miR-141-3p, miR-183-5p, miR-200a-5p, miR-205-5p, miR-429, miR-382-5p and miR-485-3p, with the last two downregulated. GO and KEGG analysis by mirPath indicated that these differentially expressed miRNAs were enriched in cell survival, apoptosis, proliferation, and differentiation. Conclusions: Coronary artery disease patients showed differential epicardial adipose tissue exosomal miRNA expression compared with patients without coronary artery disease. The results provide clues for further studies of mechanisms of atherosclerosis.

Circulating miR-183-5p levels are positively associated with the presence and severity of coronary artery disease

“…Similarly, elevated miR-183 levels were detected in the plasma exosome from patients with MI than in healthy individuals, which positively correlated with the degree of myocardial injury (14). Recently, Liu found that exosomal miR-183-5p from epicardial adipose tissue of patients with CAD were increased compared with those without CAD (25). Interestingly, Tong et al found that plasma miR-183-5p levels were novel diagnostic markers only for NSTEMI, but not for STEMI (15).…”

circSnd1 promotes atherosclerosis progression through the miR-485-3p/Olr1 signaling pathway

“…This finding is to some extent consistent with other reports. It was previously proven that in patients with coronary atherosclerosis, the level of exosomal miR-485-3p derived from epicardial adipose tissue was reduced, and in ox-LDL-treated RAW 264.7 cells, miR-485-3p was significantly decreased (according to GSE99685) [ 28 , 29 ]. However, a possibly contrary finding also exists.…”

The Role of Epicardial Adipose Tissue-Derived MicroRNAs in the Regulation of Cardiovascular Disease: A Narrative Review

“…According to one of such studies that profiled EAT-derived exosomal miRNAs in CAD patients, 53 EAT-specific miRNAs were differentially expressed (adjusted p < 0.05, fold change > 2), of which 32 miRNAs were upregulated, while 21 of them were downregulated [ 128 ]. Among these, the increases in miR-141-3p, miR-183-5p, miR-200a-5p, miR-205-5p, and miR-429, as well as the decreases in miR-382-5p and miR-485-3p were further validated by quantitative polymerase chain reaction (qPCR).…”