Thrombotic Regulation From the Endothelial Cell Perspectives.
Thrombotic Regulation From the Endothelial Cell Perspectives.
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从内皮细胞的角度来看血栓形成的调节
DOI：
10.1161/atvbaha.118.310367
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发表时间：
2018-06
期刊：
影响因子：
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通讯作者：
Early Career Committee
中科院分区：
文献类型：
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作者：
Wang M;Hao H;Leeper NJ;Zhu L;Early Career Committee
Wang等人血栓形成中的内皮细胞e91内皮TF可能在病理生理条件下增强，16、17和ECs被发现能够分泌富含TF的微粒。 18 事实上，内皮衍生的 TF 在功能上参与血栓形成。 19-24 在这方面，Witkowski 等人25 发现循环中的 miR-126（主要由 EC 产生）26 通过降低 TF mRNA 和蛋白的表达来减轻血栓形成。他们的研究表明，糖尿病患者血浆 miR-126 水平与血浆 TF 浓度和活性呈负相关。此外，抗糖尿病治疗增加了 miR-126 的水平，同时降低了血浆 TF 的水平，表明临床条件下 miR-126 对血浆 TF 的负调节。最后，通过在人微血管 EC 中处理 miR-126，他们发现 miR-126 确实通过与 TF mRNA 的 F3-3' 非翻译区相互作用来负向调节 TF 表达。这项研究揭示了通过 miR-126 表达内皮 TF 的新机制，并表明调节内皮 TF 具有预防代谢性疾病或高危患者血栓栓塞事件的潜力。然而，TF 途径抑制剂 (TFPI) 是主要的内源性抗凝蛋白。它通过直接抑制因子 Xa (FXa) 来抑制 TF 激活，并且 Fxa 依赖性地阻止因子 VIIa/TF 活性。 27 TFPI 的选择性剪接同工型在 EC、血小板和血浆中差异表达。 TFPIβ 同种型定位于内皮表面，是启动血液凝固的 TF-VIIa 复合物的有效抑制剂。在促凝条件下，如动脉粥样硬化斑块，TFPI 与 TF 共定位，表明 TFPI 在减弱 TF 活性方面发挥着积极作用。 28 艾伦·马斯特29
Wang et al Endothelium in Thrombosis e91 endothelial TF may be enhanced in pathophysiological conditions, 16, 17 and ECs were found to be able to secret microparticles rich in TF. 18 Indeed, endothelium-derived TF functionally participates in thrombosis. 19–24 In this regard, Witkowski et al25 identified that circulating miR-126, which was primarily produced by ECs, 26 attenuated thrombosis via decreasing the expression of both mRNA and protein of TF. Their study showed that levels of plasma miR-126 were negatively correlated with concentrations and activities of plasma TF in diabetic patients. Furthermore, antidiabetic treatment increased the levels of miR-126 while decreased the levels of plasma TF, indicating a negative modulation of plasma TF by miR-126 in clinical conditions. Finally, by treatment of miR-126 in human microvascular ECs, they revealed that miR-126 indeed negatively regulated TF expression via interacting with the F3-3′-untranslated region of the TF mRNA. This study uncovers a novel mechanism of endothelial TF expression via miR-126 and suggests potential of modulating endothelial TF to prevent thromboembolic events in patients with metabolic diseases or at risk.However, TF pathway inhibitor (TFPI) is the major endogenous anticoagulant protein. It inhibits TF activation by directly inhibiting factor Xa (FXa), and Fxa dependently prevents factor VIIa/TF activities. 27 Alternatively spliced isoforms of TFPI are differentially expressed by ECs and platelets and plasma. The TFPIβ isoform localizes to the endothelium surface where it is a potent inhibitor of TF–VIIa complex that initiates blood coagulation. In procoagulating conditions, like atherosclerotic plaques, TFPI colocalizes with TF, indicating an active role of TFPI in attenuating TF activity. 28 Alan Mast29