Emerging Mechanisms of Abdominal Aortic Aneurysm

Abdominal aortic aneurysm (AAA) is a progressive and often fatal vascular disease for which effective pharmacological therapies are lacking. This review synthesizes recent mechanistic advances in AAA pathogenesis and evaluates their translational significance for therapeutic development. Single-cell and spatial transcriptomic findings have delineated marked cellular heterogeneity within aneurysmal tissue, revealing dynamic interactions among vascular and immune cell populations. Vascular smooth muscle cell phenotypic modulation and programmed cell death compromise aortic wall integrity, while endothelial dysfunction promotes leukocyte recruitment and mediates early vascular responses. Infiltrating macrophages, neutrophils, and adaptive immune cells orchestrate chronic inflammation and extracellular matrix degeneration, whereas eosinophils and regulatory T cells exert context-dependent protective effects. Local factors, including intraluminal thrombus and perivascular adipose tissue, as well as systemic modulators such as dyslipidemia, gut microbiota, and sex hormones, further shape disease initiation and progression. These mechanistic insights have identified novel therapeutic targets, including inhibitors of regulated cell death, immunomodulatory agents, lipid-lowering interventions, and microbiome-directed strategies, and potential biomarkers for earlier diagnosis and improved risk stratification. Emerging mechanistic insights have highlighted the complex interplay among vascular cells, immune cells, the local microenvironment, and systemic modulators in the pathogenesis of AAA. Integrating mechanistic insights with translational research will be crucial in developing targeted interventions that pave the way for effective AAA therapies.