Singh Sandeep, de Ronde Maurice W J, Kok Maayke G M, Beijk Marcel Am, De Winter Robbert J, van der Wal Allard C, Sondermeijer Brigitte M, Meijers Joost C M, Creemers Esther E, Pinto-Sietsma Sara-Joan
Department of Vascular Medicine, Amsterdam UMC, Location AMC, The University of Amsterdam, Amsterdam, The Netherlands.
Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, Location AMC, The University of Amsterdam, Amsterdam, The Netherlands.
Open Heart. 2020 Jun;7(1). doi: 10.1136/openhrt-2019-001223.
In this study, we discovered and validated candidate microRNA (miRNA) biomarkers for coronary artery disease (CAD).
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.
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.
In conclusion, miR-122-5p and miR-223-3p might be markers of plaque instability.
在本研究中，我们发现并验证了冠状动脉疾病（CAD）的候选微小RNA（miRNA）生物标志物。
通过基于定量聚合酶链反应（qPCR）的阵列，从稳定型冠状动脉疾病（SCAD）患者（n = 14）和不稳定型冠状动脉疾病（UCAD）患者（n = 25）的动脉粥样硬化斑块材料中发现候选组织来源的miRNA。我们分别在两个大型队列（n = 395和n = 1000）的SCAD、UCAD患者以及亚临床动脉粥样硬化（SubA）患者和对照者的血清中，验证差异表达的miRNA以及文献中七个有前景的CAD相关miRNA。
在斑块材料（发现阶段）中，miR - 125b - 5p和miR - 193b - 3p在SCAD中上调最为明显，而miR - 223 - 3p和miR - 142 - 3p在UCAD患者中上调最为明显。随后在UCAD、SCAD、SubA患者和对照者血清中的验证表明，miR - 223 - 3p、miR - 133a - 3p、miR - 146 - 3p和miR - 155 - 5p显著上调。与其他组（SCAD的比值比（OR）为20.63（95%置信区间（CI）为11.16至38.15），SubA的OR为96.10（95%CI为40.13至230.14），对照者的OR为15.73（95%CI为7.80至31.72））相比，与缺血相关的miR - 499 - 5p在UCAD患者中也高度上调。然而，在SCAD、SubA和对照者之间未观察到miR - 499 - 5p表达的显著差异。miR - 122 - 5p是唯一在UCAD和SCAD患者血清中均显著上调的miRNA。
总之，miR - 122 - 5p和miR - 223 - 3p可能是斑块不稳定的标志物。
