腹主动脉瘤壁的促炎和趋化细胞因子微环境：一项蛋白质阵列研究。

The pro-inflammatory and chemotactic cytokine microenvironment of the abdominal aortic aneurysm wall: a protein array study.

作者信息

Middleton Rachel K, Lloyd Geraint M, Bown Matthew J, Cooper Nicola J, London Nicholas J, Sayers Robert D

机构信息

Vascular Surgery Group, Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.

出版信息

J Vasc Surg. 2007 Mar;45(3):574-80. doi: 10.1016/j.jvs.2006.11.020.

DOI:10.1016/j.jvs.2006.11.020

PMID:17321344

Abstract

OBJECTIVE

Cytokines are inflammatory mediators implicated in abdominal aortic aneurysm (AAA) pathogenesis. The cytokine expression profile of the AAA is poorly defined and has focused on the expression of pro-inflammatory cytokines, at the expense of chemokines and growth factors. This study aims to investigate the cytokine expression profile of the established AAA wall.

METHODS

Cytokine protein expression was measured in homogenized human aortic tissue (10 AAAs and 9 nonaneurysmal controls) using a 42-cytokine antibody-based protein array. Data were quantified using densitometric analysis and statistically analyzed using a Mann-Whitney U test.

RESULTS

A significant difference in cytokine expression between AAA and control samples was found in 15 of 42 cytokines. Several pro-inflammatory cytokines were upregulated within the AAA compared with the control: interleukin (IL)-6 (P = .001), IL-1alpha (P = .001), IL-1beta (P < .001), tumor necrosis factor (TNF)-alpha (P = .002), TNF-beta (P = .002), and oncostatin M (P = .007). The anti-inflammatory cytokine IL-10 was also upregulated (P = .002). Members of the chemokine family were also highly expressed within AAA samples: IL-8 (P = .001), epithelial neutrophil-activating peptide-78 (ENA-78; P = .006), growth related oncogene (GRO; P < .001), monocyte chemoattractant protein (MCP)-1 (P = .003), MCP-2 (P < .001), and regulated upon activation, normal T-cell expressed and secreted (RANTES; P = .001). Of the growth factors examined, granulocyte colony-stimulating factor (GCSF; P = .003) and macrophage colony-stimulating factor (MCSF; P = .004) were significantly higher in the AAA.

CONCLUSIONS

The established AAA is characterized by a distinct cytokine profile consisting of pro-inflammatory cytokines, chemokines, and specific growth factors. This suggests that these cytokines may contribute to pathologic changes within the established, preruptured aneurysm.

摘要

目的

细胞因子是参与腹主动脉瘤（AAA）发病机制的炎症介质。AAA的细胞因子表达谱定义不清，且主要集中在促炎细胞因子的表达上，而忽视了趋化因子和生长因子。本研究旨在调查已形成的AAA壁的细胞因子表达谱。

方法

使用基于42种细胞因子抗体的蛋白质阵列，测定人主动脉组织匀浆（10个AAA样本和9个非动脉瘤对照样本）中的细胞因子蛋白表达。数据采用光密度分析进行定量，并使用Mann-Whitney U检验进行统计分析。

结果

在42种细胞因子中，发现15种细胞因子在AAA样本和对照样本之间存在显著表达差异。与对照相比，AAA内几种促炎细胞因子上调：白细胞介素（IL）-6（P = 0.001）、IL-1α（P = 0.001）、IL-1β（P < 0.001）、肿瘤坏死因子（TNF）-α（P = 0.002）、TNF-β（P = 0.002）和制瘤素M（P = 0.007）。抗炎细胞因子IL-10也上调（P = 0.002）。趋化因子家族成员在AAA样本中也高度表达：IL-⑧（P = 0.001）、上皮中性粒细胞激活肽-78（ENA-78；P = 0.006）、生长相关癌基因（GRO；P < 0.001）、单核细胞趋化蛋白（MCP）-1（P = 0.003）、MCP-2（P < 0.001）以及激活后正常T细胞表达和分泌的调节因子（RANTES；P = 0.001）。在所检测的生长因子中，粒细胞集落刺激因子（GCSF；P = 0.003）和巨噬细胞集落刺激因子（MCSF；P = 0.004）在AAA中显著升高。