Tissue factor is induced by interleukin-33 in human endothelial cells: a new link between coagulation and inflammation.
Tissue factor is induced by interleukin-33 in human endothelial cells: a new link between coagulation and inflammation.
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DOI：
10.1038/srep25171
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发表时间：
2016-05-04
影响因子：
4.6
通讯作者：
Wojta J
中科院分区：
文献类型：
--
作者：
Stojkovic S;Kaun C;Basilio J;Rauscher S;Hell L;Krychtiuk KA;Bonstingl C;de Martin R;Gröger M;Ay C;Holnthoner W;Eppel W;Neumayer C;Huk I;Huber K;Demyanets S;Wojta J
组织因子(Tf)是凝血的主要触发因子。动脉粥样硬化斑块中发现高水平的转铁蛋白，当斑块破裂时，转铁蛋白释放会导致血栓形成。白介素33(IL-33)可诱导血管生成和内皮细胞的炎症激活。在这里，我们研究了IL-33对人内皮细胞转铁蛋白的影响，作为炎症和凝血之间可能的新联系。IL-33可诱导人脐静脉内皮细胞和冠状动脉内皮细胞表达Tf基因和蛋白。IL-33诱导的Tf表达依赖于ST2和NF-κB，但不依赖于IL-1。IL-33还可增加内皮细胞表面的转铁蛋白活性和内皮细胞来源的微粒中的转铁蛋白活性。IL-33处理的内皮细胞减少了全血和血浆的凝血时间，但对凝血因子VII缺乏的血浆没有影响。在人颈动脉粥样硬化斑块(n = 57)中，TFm RNA与IL-33m RNA的表达呈正相关(r = 0.691，p <； 0.001)。免疫荧光法检测到内皮细胞和血管内皮细胞表达IL-33和TF蛋白。此外，在症状性颈动脉狭窄患者的斑块中，IL-33和TF蛋白共定位于微血管内的血栓形成部位。IL-33通过诱导内皮细胞转铁蛋白的产生，增强内皮细胞的血栓形成能力，从而可能影响动脉粥样硬化环境下血栓的形成。
Tissue factor (TF) is the primary trigger of coagulation. Elevated levels of TF are found in atherosclerotic plaques, and TF leads to thrombus formation when released upon plaque rupture. Interleukin (IL)-33 was previously shown to induce angiogenesis and inflammatory activation of endothelial cells (ECs). Here, we investigated the impact of IL-33 on TF in human ECs, as a possible new link between inflammation and coagulation. IL-33 induced TF mRNA and protein in human umbilical vein ECs and coronary artery ECs. IL-33-induced TF expression was ST2- and NF-κB-dependent, but IL-1-independent. IL-33 also increased cell surface TF activity in ECs and TF activity in ECs-derived microparticles. IL-33-treated ECs reduced coagulation time of whole blood and plasma but not of factor VII-deficient plasma. In human carotid atherosclerotic plaques (n = 57), TF mRNA positively correlated with IL-33 mRNA expression (r = 0.691, p < 0.001). In this tissue, IL-33 and TF protein was detected in ECs and smooth muscle cells by immunofluorescence. Furthermore, IL-33 and TF protein co-localized at the site of clot formation within microvessels in plaques of patients with symptomatic carotid stenosis. Through induction of TF in ECs, IL-33 could enhance their thrombotic capacity and thereby might impact on thrombus formation in the setting of atherosclerosis.