Article

Plasma miR-142 predicts major adverse cardiovascular events as an intermediate biomarker of dual antiplatelet therapy

Qian-jie Tang1,2,3, He-ping Lei1,2, Hong Wu4, Ji-yan Chen1,2, Chun-yu Deng1,2, Wang-sheng Sheng1, Yong-heng Fu1,2, Xiao-hong Li1,2, Yu-bi Lin1,2, Ya-ling Han5, Shi-long Zhong1,2
1 Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
2 Medical School of South China University of Technology, Guangzhou, China
3 Department of Pharmacy, Guangdong Women and Children Hospital, Guangzhou, China
4 Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
5 Cardiovascular Research Institute and Department of Cardiology, Shenyang Northern Hospital, Shenyang, China
Correspondence to: Ya-ling Han: hanyaling@263.net, Shi-long Zhong: zhongsl@hotmail.com,
DOI: 10.1038/s41401-018-0041-7
Received: 26 December 2017
Accepted: 6 April 2018
Advance online: 11 June 2018

Abstract

MicroRNAs (miRNAs) are widely expressed in organisms and are implicated in the regulation of most biological functions. The present study investigated the association of plasma miRNAs with the clinical outcomes of dual antiplatelet therapy in coronary artery disease (CAD) patients who underwent percutaneous coronary intervention (PCI). Plasma miRNA levels were screened using high-throughput Illumina sequencing to evaluate the antiplatelet efficacy of clopidogrel and aspirin. Six plasma miRNAs (miR-126, miR-130a, miR-27a, miR-106a, miR-21, and miR-142) were associated with clopidogrel-treated platelet aggregation. These miRNAs were validated in a prospective cohort of 1230 CAD patients using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). High plasma miR-142 levels were associated with a high risk of major adverse cardiovascular events (MACE), with a hazard ratio (95% confidence interval) of 1.83 (1.30–2.59) at a false discovery rate of <5%. Multivariable Cox regression analysis revealed that diabetes mellitus, heart failure, calcium channel blocker application, and a high plasma miR-142 level were independent risk factors of MACE. The levels of the six plasma miRNAs were not significantly associated with bleeding events during the 3-year follow-up. In conclusion, plasma miR-142 is potential marker to predict MACE in CAD patients after PCI.
Keywords: plasma miRNAs; miR-142; antiplatelet therapy; MACEs; coronary artery disease

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