An investigation into the cytokine expression profile of the abdominal aortic aneurysm wall

Abdominal aortic aneurysm is a disease commonly found in elderly males involving dilatation of the abdominal aorta. The aneurysm wall is characterised by a decrease in the elastin/collagen ratio, apoptosis of smooth muscle cells and a prominent inflammatory infiltrate. Degradation of the extracellular matrix has been attributed to matrix metalloproteinases (MMP), the expression and activation of which is tightly regulated by inflammatory mediators such as cytokines. The presence of an inflammatory infiltrate is a potential source of cytokines within the aneurysm wall.;The aim of this thesis is to investigate the nature of the cytokines that are expressed within the aneurysm. Further work aims to characterise the expression of key cytokines and to investigate their effect on MMP expression.;The cytokine profile of the aneurysm wall was measured using a 42-cytokine protein array. Overall, a number of pro-inflammatory cytokines, chemokines and growth factors were raised within the aneurysm wall. Interleukin-6 (IL-), IL-8, monocyte chemoattractant protein-1 (MCP-) and MCP-2 were highly elevated in the aneurysm above the physiological levels found in abdominal and thoracic aorta.;The expression of chemokines within the aneurysm wall was characterised further using immunohistochemistry. IL-8 was found to co-localise with the infiltrate, which was predominantly formed from CD20+ B-lymphocytes and CD3+ T-lymphocytes, whilst MCP-1 co-localised to CD68+ macrophages.;The effect of IL-8 on the expression of MMP-2 and MMP-9 was investigated through an in vitro aneurysm model. The results showed that MMP-2 was expressed constitutively, whilst MMP-9 expression from the same culture decreased with time. IL-8 did not effect MMP-2 and MMP-9 expression.;In conclusion, the abdominal aortic aneurysm wall is a highly pro-inflammatory and chemotactic environment. Co-localisation of IL-8 and MCP-1 with the infiltrating cells suggests a role for these cytokines in aneurysm pathogenesis. However, a direct involvement between IL-8 and MMP expression is unlikely.