Serum amyloid A may potentiate prothrombotic and proinflammatory events in acute coronary syndromes
Serum amyloid A may potentiate prothrombotic and proinflammatory events in acute coronary syndromes
复制标题
DOI：
10.1016/j.atherosclerosis.2008.04.049
复制
发表时间：
2009-02-01
期刊：
影响因子：
5.3
通讯作者：
Ben Freedman, S.
中科院分区：
文献类型：
--
作者：
Song, Changjie;Shen, Ying;Ben Freedman, S.
目的：血清淀粉样蛋白A（SAA）水平升高，如C反应蛋白（CRP），预测冠状动脉事件。两者都诱导单核细胞组织因子（TF），并且来自冠状动脉疾病（CAD）患者的外周血单核细胞（PBMC）响应于CRP表达更高的TF。本研究探讨SAA诱导TF和肿瘤坏死因子-α（TNF）在PBMC从CAD患者和单核细胞THP-1 cells.Methods和结果：PBMC从26名男性CAD（15稳定型心绞痛，SA，和11急性冠脉综合征，ACS）和14名男性对照刺激SAA。SAA促进患者PBMC上TF活性增加高达6倍（凝血试验），与TF mRNA和蛋白质升高相关。当单核细胞粘附时PBMC反应最佳。与CRP不同，SAA在THP-1细胞中诱导TF和TNF。SAA诱导的TNF被HDL剂量依赖性地抑制。ACS患者外周血单个核细胞表达基础TF（257.4 +/- 46.8 mU/10（6）PBMC vs. 131.0 +/- 12.5 mU/10（6）PBMC，P=0.003），SAA诱导的TF高于对照细胞，而SA和对照之间没有发现差异（ACS 2246 +/- 493，SA 1364 +/- 206，对照1091 +/- 113 mU/10（6）PBMC，SAA 250 ng/mL，在剂量范围内，ACS与对照相比P=0.002）。重要的是，ACS患者中SAA诱导的TNF水平（ELISA）远高于SA或对照组（ACS 211 +/- 41，SA 108 +/- 16，对照组73 +/- 11 pg/mL，SAA 250 ng/mL，在剂量范围内，P=0.001 ACS vs.对照组或P=0.013 ACS vs. SA）。SAA诱导的TF和TNF与血清SAA水平呈正相关，在CAD，但没有controls.Conclusions：SAA是一个血栓形成和炎症介质在ACS，这可能有助于动脉粥样硬化及其并发症。(c)2008爱思唯尔爱尔兰有限公司保留所有权利。
Aims: Elevated serum amyloid A (SAA) levels, like C-reactive protein (CRP), predict coronary events. Both induce monocyte tissue factor (TF), and peripheral blood mononuclear cells (PBMC) from patients with coronary artery disease (CAD) express higher TF in response to CRP. This study examined SAA induction of TF and tumour necrosis factor-alpha (TNF) in PBMC from patients with CAD and in monocytoid THP-1 cells.Methods and results: PBMC from 26 males with CAD (15 stable angina, SA, and 11 acute coronary syndromes, ACS) and 14 male controls were stimulated with SAA. SAA promoted up to six-fold increase in TF activity (recalcification assay) on PBMC from patients, associated with elevated TF mRNA and protein. PBMC responded optimally when monocytes were adherent. Unlike CRP, SAA induced TF and TNF in THP-1 cells. SAA-induced TNF was dose-dependently inhibited by HDL. PBMC from patients with ACS expressed more basal TF (257.4 +/- 46.8 mU/10(6) PBMC vs. 131.0 +/- 12.5 mU/10(6) PBMC, P=0.003), and greater SAA-induced TF than cells from controls, whereas no difference was found between SA and controls (ACS 2246 +/- 493, SA 1364 +/- 206, controls 1091 +/- 113 mU/10(6) PBMC, with SAA 250 ng/mL, P=0.002 ACS vs. controls across the dose range). Importantly, SAA-induced TNF levels (ELISA) were much higher in patients with ACS than SA or controls (ACS 211 +/- 41, SA 108 +/- 16, controls 73 +/- 11 pg/mL, with SAA 250 ng/mL, P=0.001 ACS vs. controls or P=0.013 ACS vs. SA across the dose range). SAA-induced TF and TNF correlated positively with serum SAA levels in CAD, but not controls.Conclusions: SAA is a prothrombotic and proinflammatory mediator in ACS which may contribute to atherogenesis and its complications. (c) 2008 Elsevier Ireland Ltd. All rights reserved.