Vascular Biology Unit, Department of Surgery, School of Medicine, James Cook University, Townsville, QLD, Australia.
Am J Pathol. 2010 May;176(5):2098-106. doi: 10.2353/ajpath.2010.090416. Epub 2010 Mar 26.
The aim of this study was to examine aortic biopsies with a cytokine array to identify new cytokines associated with abdominal aortic aneurysm (AAA). We assessed the relative expression of 79 cytokines using antibody-based cytokine arrays in a total of 12 AAA and 12 control aortic biopsies. Based on these findings we validated the findings for one cytokine by examining a further 11 AAA and 11 atherothrombosis biopsies and serum from 1028 men, 315 of whom had an AAA. Three cytokines (interleukins 1B and 8, and Chemokine CC motif ligand 22 [CCL22]) were consistently up-regulated in AAA biopsies. Since CCL22 had not previously been associated with aortic dilatation, we confirmed the upregulation of this cytokine in further tissue biopsies and serum using enzyme-linked immunosorbent assay. Median serum concentrations of CCL22 were greater in men with AAA (0.69 ng/ml) than controls (0.56 ng/ml, P < 0.01). Serum CCL22 was independently associated with both small (OR 1.51, 95% CI 1.21-1.88) and large AAA (OR 1.33, 95% CI 1.08-1.62) after adjusting for other risk factors. The association between CCL22 and AAA was also confirmed using immunohistochemistry. The results presented in this study demonstrate a novel association between CCL22 and AAA as well as illustrate how a protein array can be used to identify novel markers of potential pathogenic and diagnostic significance for AAA.
本研究旨在通过细胞因子阵列检查主动脉活检,以鉴定与腹主动脉瘤(AAA)相关的新细胞因子。我们使用基于抗体的细胞因子阵列评估了总共 12 个 AAA 和 12 个对照主动脉活检中的 79 种细胞因子的相对表达。根据这些发现,我们通过进一步检查 11 个 AAA 和 11 个动脉粥样硬化血栓形成活检以及来自 1028 名男性的血清(其中 315 名患有 AAA)来验证一种细胞因子的发现。三种细胞因子(白细胞介素 1B 和 8 以及趋化因子 CC 基序配体 22 [CCL22])在 AAA 活检中始终上调。由于 CCL22 以前与主动脉扩张无关,因此我们使用酶联免疫吸附试验进一步确认了该细胞因子在其他组织活检和血清中的上调。AAA 男性的 CCL22 中位数血清浓度(0.69 ng/ml)高于对照组(0.56 ng/ml,P <0.01)。在校正其他危险因素后,血清 CCL22 与小(OR 1.51,95%CI 1.21-1.88)和大 AAA(OR 1.33,95%CI 1.08-1.62)均独立相关。使用免疫组织化学也证实了 CCL22 与 AAA 之间的关联。本研究中的结果表明 CCL22 与 AAA 之间存在新的关联,并说明了蛋白质阵列如何用于鉴定 AAA 潜在致病和诊断意义的新标志物。