microRNA-19b 通过靶向组织因子在不稳定型心绞痛患者中发挥潜在的抗血栓保护作用。

MicroRNA-19b functions as potential anti-thrombotic protector in patients with unstable angina by targeting tissue factor.

机构信息

Department of Cardiology, Peking University People's Hospital, Beijing, China.

Department of Medicine, Karolinska Institutet, Stockholm, Sweden.

出版信息

J Mol Cell Cardiol. 2014 Oct;75:49-57. doi: 10.1016/j.yjmcc.2014.06.017. Epub 2014 Jul 3.

Abstract

The activation of a hemostatic system plays a critical role in the incidence of acute coronary events. Hemostatic proteins may be regulated by microRNAs (miRNAs). Microparticles (MPs) are the major carrier of circulating miRNAs. The aim of this study was to determine the potential role of miRNAs in regulating gene expression involved in the hemostatic system in patients with unstable angina (UA). MiRNA expression profiles in the plasma from patients with UA (UA group, n=9) compared with individuals with clinical suspicion of coronary artery disease (CAD) but negative angiography (control group, n=9) showed that among 36 differentially expressed miRNAs, miR-19b was the most obvious one. Using real-time PCR, 5 selected miRNA levels in plasma (UA group, n=20; control group, n=30) and plasma MPs (UA group n=6; control group n=6) were proved to be consistent with the miRNA array. Flow cytometry analysis indicated that the amounts of plasma endothelial microparticles (EMPs) were increased in UA patients (UA group, n=4) compared to controls (control group, n=4). In cultured endothelial cells (ECs), TNF-α increased miR-19b release and expression. Tissue factor (TF) was predicted to be the target of miR-19b by bioinformatics analysis. Luciferase reporter assays demonstrated that miR-19b binds to TF mRNA. Overexpression of miR-19b inhibited TF expression and procoagulant activity. This study indicates that in UA patients, the increase of miR-19b wrapped in EMPs due to endothelial dysfunction may partially contribute to the circulating miR-19b elevation and miR-19b may play an anti-thrombotic role by inhibiting the expression of TF in ECs.

摘要

止血系统的激活在急性冠状动脉事件的发生中起着关键作用。止血蛋白可能受 microRNAs(miRNAs)调节。微粒(MPs)是循环 miRNAs 的主要载体。本研究旨在确定 miRNAs 在调节与不稳定型心绞痛(UA)患者止血系统相关基因表达中的潜在作用。与临床怀疑患有冠状动脉疾病(CAD)但血管造影阴性的个体(对照组,n=9)相比,UA 患者(UA 组,n=9)血浆中的 miRNA 表达谱显示,在 36 个差异表达的 miRNAs 中,miR-19b 最为明显。使用实时 PCR,在血浆(UA 组,n=20;对照组,n=30)和血浆 MPs(UA 组 n=6;对照组 n=6)中验证了 5 种选定的 miRNA 水平与 miRNA 阵列一致。流式细胞术分析表明,与对照组(n=4)相比,UA 患者的血浆内皮微颗粒(EMP)数量增加(UA 组,n=4)。在培养的内皮细胞(ECs)中,TNF-α增加了 miR-19b 的释放和表达。生物信息学分析预测 TF 是 miR-19b 的靶标。荧光素酶报告基因检测证实 miR-19b 结合 TF mRNA。miR-19b 的过表达抑制 TF 表达和促凝血活性。本研究表明,在 UA 患者中,由于内皮功能障碍导致 EMP 包裹的 miR-19b 增加,可能部分导致循环 miR-19b 升高,miR-19b 通过抑制 ECs 中 TF 的表达发挥抗血栓作用。

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