Human Transcriptomic Meta-Analysis Identifies Immune-Redox Remodeling and Impaired Vascular Wall Homeostasis in...

Abdominal aortic aneurysm (AAA) is a progressive vascular disease in which no pharmacological therapy has consistently reduced expansion or rupture risk, highlighting the need to better define reproducible molecular programs in human aneurysmal tissue. Publicly available human abdominal aortic tissue microarray datasets were identified using the Search, Tag, Analyze Resource for Gene Expression Omnibus (STARGEO) platform. Three independent datasets comprising 324 total samples, including 278 aneurysmal abdominal aortic tissue samples and 46 non-aneurysmal control samples, were included. Transcriptomic meta-analysis identified 2331 differentially expressed genes in AAA tissue relative to non-aneurysmal controls. Upregulated genes were enriched for immune and inflammatory signaling, oxidative stress regulation, and extracellular matrix remodeling. Downregulated genes included regulators of vascular smooth muscle cell structure, cell-matrix adhesion, cytoskeletal organization, and metabolic homeostasis. Human AAA tissue demonstrates a reproducible inflammatory-oxidative transcriptional program characterized by leukocyte recruitment, cytokine amplification, innate immune sensing, redox remodeling, protease-mediated extracellular matrix degradation, and suppression of vascular smooth muscle cell and matrix maintenance programs. These findings support a model of AAA as an immune-redox remodeling disease in which inflammatory, oxidative, proteolytic, structural, and failed resolution pathways converge to destabilize the aortic wall.