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

ObjectiveCytokines 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.MethodsCytokine 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.ResultsA 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-1α (P = .001), IL-1β (P < .001), tumor necrosis factor (TNF)-α (P = .002), TNF-β (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.ConclusionsThe 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.

Clinical RelevanceThrough the screening of the expression of 42 cytokines within the wall of large abdominal aortic aneurysms (>55 mm diameter), this study has identified a number of pro-inflammatory cytokines, chemokines, and growth factors that are raised within the aneurysm wall. This suggests that pathways involving these cytokines may be involved in aneurysm development. This study contributes to the collective understanding of the pathologic changes in the abdominal aortic aneurysm wall that may ultimately lead to the development of a nonsurgical therapeutic intervention to stabilize the abdominal aortic aneurysm, prevent further growth, and aneurysm rupture.