Atheroprotective effects of statins in patients with unstable angina by regulating the blood-borne microRNA network.
Atheroprotective effects of statins in patients with unstable angina by regulating the blood-borne microRNA network.
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他汀类药物通过调节血源性 microRNA 网络对不稳定心绞痛患者的动脉粥样硬化保护作用
DOI：
10.3892/mmr.2017.6616
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发表时间：
2017-07
影响因子：
3.4
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Li S;Cao C;Chen H;Song J;Lee C;Zhang J;Zhang F;Geng Q;Li Z;Li J
实验研究已经证明了他汀类药物在急性冠状动脉综合征（ACS）中的几种作用，这些作用可能会将其临床益处扩展到血脂改变本身之外。然而，确切的基本机制仍有待阐明。microRNA（miRNAs）在动脉粥样硬化斑块进展的病理生理学中起重要作用。本研究探讨他汀类药物通过调节循环miRNA网络对不稳定型心绞痛（UA）患者的保护作用。miRNA阵列结果显示，与非冠状动脉疾病对照组（n = 8）相比，非他汀类药物治疗的UA患者（n = 8）中有21个差异表达的miRNA，与非他汀类药物治疗的UA患者（n=8）相比，他汀类药物治疗的UA患者（n=8）中有33个差异表达的miRNA。使用TargetScan和米兰达程序来预测miRNA靶基因。基于CGAP SAGE文库，通过注释、可视化和集成发现数据库（大卫）平台对血管内皮细胞和单核细胞中的miRNA靶基因进行聚类，并且基于UP组织特异性文库，通过大卫平台对血小板中的miRNA靶基因进行聚类。通过大卫平台的PANTHER数据库用于进行信号通路分析。通过Cytoscape软件可视化miRNA-基因/通路网络。生物信息学分析表明，他汀类药物诱导的miRNAs功能主要集中在UA患者的血管生成、整合素和血小板源性生长因子信号通路中。在内皮细胞和血小板中，他汀类药物诱导的miRNA主要靶向整合素信号通路，而在单核细胞中主要靶向通过Rho GT3信号通路的细胞骨架调节。这些结果表明，他汀类药物可能通过影响循环miRNA调控网络在UA患者中发挥系统性保护作用。需要进一步的研究来验证他汀类药物诱导的miRNAs在内皮细胞、血小板和单核细胞中的功能。
Experimental studies have demonstrated several effects of statins in acute coronary syndrome (ACS) that may extend their clinical benefit beyond the lipid profile modification itself. However, the precise underlying mechanism remains to be elucidated. microRNAs (miRNAs) serve significant roles in the pathophysiology of atherosclerotic plaque progression. The present study investigated the protective role of statins in patients with unstable angina (UA) by regulating the circulating miRNA network. miRNA array results demonstrated that there were 21 differentially expressed miRNAs in non-statin-treated patients with UA (n=8) compared with non-coronary artery disease controls (n=8), and 33 differentially expressed miRNAs in statin-treated patients with UA (n=8) compared with non-statin patients. TargetScan and miRanda programs were used to predict miRNAs target genes. miRNAs target genes in vascular endothelial cells and monocytes were clustered based on the CGAP SAGE library via the Database for Annotation, Visualization and Integrated Discovery (DAVID) platform, and miRNA target genes in platelets were clustered based on a UP tissue-specific library via the DAVID platform. The PANTHER database via DAVID platform was used to perform signaling pathway analysis. The miRNA-gene/pathway network was visualized by Cytoscape software. Bioinformatic analysis suggested that statin-induced miRNAs functions were primarily enriched in angiogenesis, integrin and platelet derived growth factor signaling pathways in UA patients. In endothelial cells and platelets, statin-induced miRNAs primarily targeted the integrin signaling pathway, and in monocytes primarily targeted cytoskeletal regulation by the Rho GTPase signaling pathway. These results revealed that statins may serve systematic protective roles in UA patients by influencing the circulating miRNA regulatory network. Further studies are required to verify the functions of statin-induced miRNAs in endothelial cells, platelets and monocytes.