Thromb Haemost 2020; 120(01): 121-131
DOI: 10.1055/s-0039-1700518
New Technologies, Diagnostic Tools and Drugs
Georg Thieme Verlag KG Stuttgart · New York

PBMCs-Derived microRNA Signature as a Prethrombotic Status Discriminator in Stable Coronary Artery Disease

Jie Gao
1  Cardiovascular Diseases Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
2  China Heart Institute of Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, China
,
Jia Liu
1  Cardiovascular Diseases Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
2  China Heart Institute of Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, China
,
Ying Zhang
1  Cardiovascular Diseases Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
2  China Heart Institute of Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, China
,
BaoYi Guan
1  Cardiovascular Diseases Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
2  China Heart Institute of Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, China
,
Hua Qu
1  Cardiovascular Diseases Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
2  China Heart Institute of Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, China
,
Hua Chai
1  Cardiovascular Diseases Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
2  China Heart Institute of Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, China
,
WenTing Wang
3  Department of Graduate School, Beijing University of Chinese Medicine, Beijing, China
,
XiaoJuan Ma
1  Cardiovascular Diseases Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
2  China Heart Institute of Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, China
,
DaZhuo Shi
1  Cardiovascular Diseases Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
2  China Heart Institute of Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, China
› Author Affiliations
Funding This work was supported by the National Natural Science Foundation of China, grant no. 81573818 and 81774141 (to D.S.).
Further Information

Publication History

25 March 2019

03 September 2019

Publication Date:
12 November 2019 (online)

Abstract

Prethrombotic status (PTS) in patients with stable coronary artery disease (SCAD) increases the risk of coronary thrombosis. Accumulating evidences have indicated that micro-ribonucleic acids (miRNAs) may serve as promising biomarkers for SCAD patients with PTS. The present study aimed to identify the miRNA signature in SCAD patients with PTS and evaluated their diagnostic significance. In the screening phase, 32 differently expressed miRNAs (DEMs) in peripheral blood mononuclear cells (PBMCs) were detected in 35 SCAD patients compared with 5 healthy controls by microarray. MiRNA-gene network analysis was then performed, and 4 DEMs were selected for validation with reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) test in an independent cohort comprising 79 SCAD patients and 19 healthy controls. Compared with healthy controls, RT-qPCR test verified the upregulations of miR-34a-5p, miR-432–5p, and miR-370–3p detected by microarray; while the upregulation of miR-495–3p measured by RT-qPCR was not consistent with its low expression detected by microarray. Only miR-34a-5p and miR-495–3p were significantly upregulated in the PTS group compared with the non-PTS group (p < 0.01, p < 0.05). Receiver-operating characteristic (ROC) analysis showed that PBMCs-derived miR-34a-5p and miR-495–3p may discriminate PTS with the areas under the ROC curve (AUC) of 0.780 (confidence interval [CI]95% = 0.673–0.866) and 0.712 (CI95% = 0.599–0.808), respectively. The combination of miR-34a-5p and fibrinogen (FIB, a traditional biomarker for PTS) improved AUC to 0.885 (CI95% = 0.793–0.946) and showed added predictive ability compared with FIB, with an integrated discrimination improvement of 0.201 (p < 0.01). Therefore, the combination of miR-34a-5p and FIB may serve as an efficient tool for distinguishing PTS in SCAD patients.

Supplementary Material