Effects of statin on circulating microRNAome and predicted function regulatory network in patients with unstable angina.

Effects of statin on circulating microRNAome and predicted function regulatory network in patients with unstable angina.
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他汀类药物对不稳定心绞痛患者循环microRNAome的影响及预测功能调节网络

DOI:
10.1186/s12920-015-0082-4
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发表时间:
2015-03-13
影响因子:
2.7
通讯作者:
Xu N
Xu N
中科院分区:
医学3区
文献类型:
--
作者:
Li J;Chen H;Ren J;Song J;Zhang F;Zhang J;Lee C;Li S;Geng Q;Cao C;Xu N

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他汀类药物治疗在稳定不稳定的心绞痛(UA)患者的牙菌斑方面起着关键作用,尽管其机制在很大程度上尚未探索。 进行了miRNA阵列以比较接受(n = 10)的UA患者的循环全血miRNA特征,没有他汀类药物(n = 10)和血浆miRNA概况UA患者(n = 5)和未经汀类药物(n = n =) 10)22个全血miRNA和19个血浆miRNA在汀类药物组中明显更新。 Diana Microt,然后根据功能和细胞类型使用数据库进行注释,可视化和集成发现(David)。 = 80); Reactome数据库。 这些他汀类药物调节的靶基因主要在I)斑块巨噬细胞和血小板中表达,它们参与了单核细胞中的止血过程;整合分析表明,他汀类药物主要调节人动脉粥样硬化病变中Rho GTPase和止血的信号传导途径。 我们的研究表明,他汀类药物在UA患者的循环中诱导多个miRNA的表达,这些miRNA通过调节对UA发病机理至关重要的信号途径起着重要作用。 本文的在线版本(doi:10.1186/s12920-015-0082-4)包含补充材料,可供授权用户使用。
BackgroundStatin therapy plays a pivotal role in stabilizing the plaque for unstable angina (UA) patients although its mechanism(s) remains largely unexplored. Here we aim to identify microRNAs (miRNAs) mediating the protective effect of statins in UA patients.MethodsMiRNAs Array was carried out to compare the circulating whole blood miRNA profile of UA patients treated with (n = 10) and without statin (n = 10) and plasma miRNA profile UA patients treated with (n = 5) and without statin (n = 5). 22 whole blood miRNAs and 19 plasma miRNAs were found significantly upregulated in statin group. Targets of these miRNAs were predicted by algoritms: Targetscan, Miranda and Diana microT, then clustered according to functions and cell types by using the Database for Annotation, Visualization and Integrated Discovery (DAVID). To reveal the enriched function pathways in human atherosclerotic plaque, we analyzed microarray data from GEO database, Coronary atherosclerotic plaque (n = 80); macrophages in ruptured plaque (n = 11); carotid atheroma plaque (n = 64); advanced carotid atherosclerotic plaque (n = 29) using Reactome database. Integrated analysis indicated that statin induced miRNAs mainly regulate the signaling pathways of Rho GTPase and hemostasis in human atherosclerotic lesion. In vulnerable plaque, additional immune system signaling was also targeted.ResultsThe data showed target genes regulated by these statin induced miRNAs majorly expressed in i) plaque macrophage and platelet, where they were involved in hemostasis process; ii) in monocyte to regulate NGF apoptosis; iii) and in endothelial cell function in Rho GTPase pathway. Integrate analysis indicated that statin induced miRNAs mainly regulate the signaling pathways of Rho GTPase and hemostasis in human atherosclerotic lesion.ConclusionsOur study suggest that statin induces the expression of multiple miRNAs in the circulation of UA patient, which play important roles by regulating signal pathways critical for the pathogenesis of UA.
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