Profiling and functional characterization of circulation LncRNAs that are associated with coronary atherosclerotic plaque stability

摘要

Background: Accumulating studies have demonstrated that some long non-coding RNAs (lncRNAs) play critical roles in the pathogenesis of atherosclerosis. We aimed to identify circulation lncRNAs that are potential biomarkers to evaluate coronary atherosclerotic plaque stability. Methods and Results: The transcriptomes of blood samples of three patients with stable plaque and three patients with unstable plaque were sequenced by RNA-sequencing. A total of 62 lncRNAs were found to be differentially expressed in patients with unstable plaques. The expressions of four candidate lncRNAs (ANP32A-005, TULP4-005, PDCD4-010, and SNHG7-003) were quantified using blood samples from 15 patients with stable plaques and 15 patients with unstable plaques, subsequently. In addition, the expression levels of these four lncRNAs in LPS (lipopolysaccharide)-activated THP-1 monocytes and THP-1-derived macrophages were measured. LncRNA-SNHG7-003 was validated to be significantly down-regulated in blood samples of patients with unstable plaques and LPS-stimulated monocytes and macrophages. Moreover, plasmid-transfection mediated over-expression of SNHG7-003 markedly inhibited the activation of NF-κB pathway, and reduced the secretion of inflammatory mediators (TNF-α, IL-1β, MCP-1 and MMP-9) in LPS-activated THP-1 monocytes and macrophages. Conclusion: LncRNA-SNHG7-003 inhibits NF-κB activation and regulates inflammatory responses in human monocytes and macrophages. Blood lncRNA-SNHG7-003 is a potential biomarker for evaluating plaque stability in patients with coronary artery diseases.