The involvement of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in atherosclerosis
The involvement of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in atherosclerosis
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DOI：
10.1016/j.jacc.2004.12.065
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发表时间：
2005-04-05
影响因子：
24
通讯作者：
George, J
中科院分区：
文献类型：
--
作者：
Michowitz, Y;Goldstein, E;George, J
目的：本研究确定肿瘤坏死因子（TNF）相关凋亡诱导配体（TRAIL）在动脉粥样硬化性血管疾病中的意义。背景：炎症与动脉粥样硬化的发病机制有关。TNF相关的凋亡诱导配体/APO-2L是TNF超家族的一员，具有诱导凋亡的作用，并因其免疫调节特性而被公认。方法采用免疫印迹法和实时聚合酶链反应法，在氧化低密度脂蛋白（oxLDL）培养的外周单核细胞上检测TRAIL的诱导作用。采用酶联免疫吸附法测定动脉粥样硬化患者的可溶性TRAIL水平。结果肿瘤坏死因子相关的凋亡诱导配体存在于稳定的动脉粥样硬化病变中，在易损斑块中增加，并与CD3细胞和oxLDL共定位。氧化低密度脂蛋白培养后，外周血单核细胞中tnf相关凋亡诱导配体信使核糖核酸（mRNA）和蛋白表达上调。与稳定的动脉粥样硬化疾病患者和健康受试者相比，不稳定型心绞痛患者血清可溶性TRAIL水平显著降低，但tnf - α或fas配体水平不显著降低。外周血单核细胞中可溶性TRAIL与c反应蛋白水平呈负相关，但与TRAIL mRNA水平无负相关。结论：肿瘤坏死因子相关的凋亡诱导配体在斑块浸润的CD3细胞中表达，并由oxLDL诱导，而可溶性TRAIL水平在急性冠状动脉综合征患者中降低，且与c反应蛋白水平呈负相关。这些结果支持TRAIL在动脉粥样硬化中的可能作用。(c) 2005年由美国心脏病学会基金会提供。
OBJECTIVES Herein, we determined the significance of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in atherosclerotic vascular disease.BACKGROUND Inflammation is associated with the pathogenesis of atherosclerosis. The TNF-related apoptosis-inducing ligand/APO-2L, a member of the TNF superfamily, has a role in apoptosis induction and is recognized for its immunomodulatory properties.METHODS Stable and vulnerable atherosclerotic human plaques and aortas from atherosclerotic mice were assayed for the presence of TRAIL, and its inducibility was assayed by immunoblot and real-time polymerase chain reaction on peripheral mononuclear cells incubated with oxidized low-density hpoprotein (oxLDL). Enzyme-linked immunosorbent assay was used for the determination of soluble TRAIL levels in atherosclerotic patients.RESULTS Tumor necrosis factor-related apoptosis-inducing ligand is present in stable atherosclerotic lesions, is increased in vulnerable plaques, and is found to colocalize with CD3 cells and oxLDL. The TNF-related apoptosis-inducing ligand messenger ribonucleic acid (mRNA) and protein expression was up-regulated in peripheral blood mononuclear cells after incubation with oxLDL. Serum levels of soluble TRAIL but not TNF-alpha or Fas-ligand were reduced significantly in patients with unstable angina as compared with patients with stable atherosclerotic disease and healthy subjects. A negative correlation was demonstrated between soluble TRAIL and C-reactive protein levels but not with levels of mRNA of TRAIL in peripheral blood mononuclear cells.CONCLUSIONS Tumor necrosis factor-related apoptosis-inducing ligand is expressed in plaque-infiltrating CD3 cells and induced by oxLDL, whereas levels of soluble TRAIL are reduced in patients with acute coronary syndromes and negatively correlate with C-reactive protein levels. These results support a possible role for TRAIL in atherosclerosis. (c) 2005 by the American College of Cardiology Foundation.