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MiR-223-3p and miR-122-5p as circulating biomarkers for plaque instability

2020; BMJ; Volume: 7; Issue: 1 Linguagem: Inglês

10.1136/openhrt-2019-001223

2398-595X

Sandeep Singh, Maurice W.J. de Ronde, M. G. M. Kok, Marcel A.M. Beijk, Robbert J. de Winter, Allard C. van der Wal, Brigitte M. Sondermeijer, Joost C.M. Meijers, Esther E. Creemers, Sara‐Joan Pinto‐Sietsma,

Cancer-related molecular mechanisms research

Background In this study, we discovered and validated candidate microRNA (miRNA) biomarkers for coronary artery disease (CAD). Method Candidate tissue-derived miRNAs from atherosclerotic plaque material in patients with stable coronary artery disease (SCAD) (n=14) and unstable coronary artery disease (UCAD) (n=25) were discovered by qPCR-based arrays. We validated differentially expressed miRNAs, along with seven promising CAD-associated miRNAs from the literature, in the serum of two large cohorts (n=395 and n=1000) of patients with SCAD and UCAD and subclinical atherosclerosis (SubA) and controls, respectively. Result From plaque materials (discovery phase), miR-125b-5p and miR-193b-3p were most upregulated in SCAD, whereas miR-223-3p and miR-142-3p were most upregulated in patients with UCAD. Subsequent validation in serum from patients with UCAD, SCAD, SubA and controls demonstrated significant upregulation of miR-223-3p, miR-133a-3p, miR-146-3p and miR-155-5p. The ischaemia-related miR-499-5p was also highly upregulated in patients with UCAD compared with the other groups (SCAD OR 20.63 (95% CI 11.16 to 38.15), SubA OR 96.10 (95% CI 40.13 to 230.14) and controls OR 15.73 (95% CI 7.80 to 31.72)). However, no significant difference in miR-499-5p expression was observed across SCAD, SubA and controls. MiR-122-5p was the only miRNA to be significantly upregulated in the serum of both patients with UCAD and SCAD. Conclusion In conclusion, miR-122-5p and miR-223-3p might be markers of plaque instability.