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

与冠状动脉粥样硬化斑块稳定性相关的循环 LncRNA 的分析和功能表征

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作者:Zhicheng Pan, Zixu Fan, Jianwei Ma, Hua Liu, Linghong Shen, Ben He, Min Zhang

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.

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.

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.

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