Pathophysiology of abdominal aortic aneurysms. Schematic diagram illustrating events thought to contribute to the development and progression of AAAs. Injury to the aortic wall, either as a consequence of or in association with known risk factors (I), leads to recruitment of leukocytes into the aortic media (II), macrophage activation, and production of proinflammatory molecules (III). Macrophages also produce proenzyme forms of MMPs (pro-MMPs) (IV), which are activated in the extracellular space (V). TIMPs may neutralize MMP activity (VI), but this appears insufficient to prevent degradation of structural matrix proteins (elastin and interstitial collagens) (VII). Over a period of years, elastin degradation, cyclic strain, and elevated wall tension bring about progressive aortic dilatation (VIII). Collagen degradation further weakens the aortic wall (IX); although medial SMCs and fibroblasts might promote structural repair, apoptosis and cellular senescence cause SMC depletion (X), and interstitial collagen appears disorganized (XI). Aneurysm tissues exhibit infiltration by T cells, B lymphocytes, plasma cells, and DCs and local deposition of immunoglobulins, reflecting a cellular and humoral immune response (XII). Understanding the adaptive cellular immune response in AAAs may reveal how different T cell subsets (i.e., Th1 versus Th2) interact with macrophages to promote or suppress aneurysmal degeneration, based on the local balance of proinflammatory (XIII) and anti-inflammatory (XIV) molecules. Some cytokines produced within aneurysm tissue, such as IL-6 and IFN-γ, may have dual and opposing functions depending on the specific context (XV). EDPs, elastin degradation peptides; MPh, macrophages; PGs, prostaglandins; ROS, reactive oxygen species.