Circulating 'lncRNA OTTHUMT00000387022' from monocytes as a novel biomarker for coronary artery disease

被引：90

作者：

Cai, Yue ^{[1
,2
]}

Yang, Yujia ^{[1
,2
,3
]}

Chen, Xiongwen ^{[1
,4
,5
]}

Wu, Genze ^{[1
,2
]}

Zhang, Xiaoqun ^{[1
,2
]}

Liu, Yukai ^{[1
,2
]}

Yu, Junyi ^{[1
,2
]}

Wang, Xinquan ^{[1
,2
]}

Fu, Jinjuan ^{[1
,2
]}

Li, Chuanwei ^{[1
,2
]}

Jose, Pedro A. ^{[6
,7
]}

Zeng, Chunyu ^{[1
,2
]}

Zhou, Lin ^{[1
,2
]}

机构：

[1] Third Mil Med Univ, Daping Hosp, Dept Cardiol, Chongqing, Peoples R China

[2] Chongqing Inst Cardiol, Chongqing, Peoples R China

[3] Third Mil Med Univ, Daping Hosp, Dept Neurol, Chongqing, Peoples R China

[4] Temple Univ, Cardiovasc Res Ctr, Sch Med, Philadelphia, PA 19122 USA

[5] Temple Univ, Dept Physiol, Sch Med, Philadelphia, PA 19122 USA

[6] Univ Maryland, Sch Med, Dept Med, Div Neurol, Baltimore, MD 21201 USA

[7] Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA

来源：

CARDIOVASCULAR RESEARCH | 2016年 / 112卷 / 03期

基金：

中国国家自然科学基金;

关键词：

Long non-coding RNAs; Coronary artery disease; Biomarker; Blood monocyte; LONG NONCODING RNA; CELL-PROLIFERATION; POOR-PROGNOSIS; EXPRESSION; HEART; ASSOCIATION; RISK; ATHEROSCLEROSIS; IDENTIFICATION; INFLAMMATION;

D O I：

10.1093/cvr/cvw022

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Aims Long non-coding RNAs (lncRNAs) have been found to be involved in the pathogenesis of coronary artery disease (CAD). However, it remains to be established whether or not circulating lncRNAs can serve as biomarkers of CAD. Methods and results Using a microarray-based lncRNA expression profiling, we found 86 lncRNAs that were differentially expressed in circulating peripheral blood monocytes and plasma from 15 CAD patients and 15 control subjects. After choosing a consistent criterion (average normalized intensity >= 7 with significance,0.005) and confirmed by quantitative PCR, only three lncRNAs (CoroMarker, BAT5, and IL21R-AS1) remained as candidate CAD biomarkers. Using the analysis of area under the curve (AUC) of the receiver-operating characteristic in another pilot group and another larger cohort, CoroMarker was found to be the best candidate biomarker for CAD with an AUC of 0.920 and 95% confidence interval of 0.892-0.947. CoroMarker was independent from known CAD risk factors and other cardiovascular diseases. In a prospective study, we found that the sensitivity and specificity of CoroMarker were 76 and 92.5%, respectively. Functional enrichment analysis showed CoroMarker to be clustered with genes positively associated with signal transduction, transmembrane transport, synaptic transmission, and innate immunity and negatively associated with inflammation. These findings were validated in THP-1 cells; CoroMarker siRNA treatment decreased the concentrations of proinflammatory cytokines [interleukin (IL)-1 beta, IL-6, and tumour necrosis factor alpha] in the culture medium. Conclusion The present study suggests that CoroMarker is a novel and specific biomarker of CAD.

引用

页码：714 / 724

页数：11

共 58 条

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