长戊氧嘧啶PTX3上调人内皮细胞组织因子表达:血管炎症和凝血激活之间的新联系

E. Napoleone, A. Di Santo, A. Bastone, G. Peri, A. Mantovani, G. de Gaetano, M. Donati, R. Lorenzet
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引用次数: 162

摘要

炎症是动脉粥样硬化斑块发展和缺血性心脏病的主要因素。PTX3是一种长链戊氧嘧啶,最近在急性心肌梗死患者中被发现增加。由于组织因子(tissue factor, TF)是体内血液凝固的触发因子,在斑块破裂后血栓形成中起主导作用,因此我们测试了PTX3调节TF表达的可能性。人脐静脉内皮细胞,与内毒素(脂多糖)或炎症细胞因子白介素-1孵育;肿瘤坏死因子-&agr;表达TF。PTX3的存在以剂量依赖的方式使TF活性和抗原增加数倍。PTX3在转录水平上发挥作用,因为在PTX3存在的情况下,刺激介导的TF mRNA水平升高。PTX3测定的mRNA的增加源于交易因子c-Rel/p65的核结合活性增强,这是由激动剂介导的,并通过电泳迁移位移法测量。c-Rel/p65活性增加的机制在于c-Rel/p65抑制蛋白的降解增强。在血管损伤区域,在炎症反应期间,细胞介导的纤维蛋白沉积发生。我们的研究结果表明,PTX3通过增加TF的表达,可能在血栓形成和缺血性血管疾病中发挥作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Long Pentraxin PTX3 Upregulates Tissue Factor Expression in Human Endothelial Cells: A Novel Link Between Vascular Inflammation and Clotting Activation
Inflammation is a major contributing factor to atherosclerotic plaque development and ischemic heart disease. PTX3 is a long pentraxin that was recently found to be increased in patients with acute myocardial infarction. Because tissue factor (TF), the in vivo trigger of blood coagulation, plays a dominant role in thrombus formation after plaque rupture, we tested the possibility that PTX3 could modulate TF expression. Human umbilical vein endothelial cells, incubated with endotoxin (lipopolysaccharide) or the inflammatory cytokines interleukin-1&bgr; and tumor necrosis factor-&agr;, expressed TF. The presence of PTX3 increased TF activity and antigen severalfold in a dose-dependent fashion. PTX3 exerted its effect at the transcription level, inasmuch as the increased levels of TF mRNA, mediated by the stimuli, were enhanced in its presence. The increase in mRNA determined by PTX3 originated from an enhanced nuclear binding activity of the transacting factor c-Rel/p65, which was mediated by the agonists and measured by electrophoretic mobility shift assay. The mechanism underlying the increased c-Rel/p65 activity resided in an enhanced degradation of the c-Rel/p65 inhibitory protein I&kgr;B&agr;. In the area of vascular injury, during the inflammatory response, cell-mediated fibrin deposition takes place. Our results suggest that PTX3, by increasing TF expression, potentially plays a role in thrombogenesis and ischemic vascular disease.
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