Abdominal Aortic Aneurysm Beyond Diameter: An Exploratory Cross-Dataset Analysis of Transcriptomic Programs Associated with Size, Rupture, and Regional Wall Stress

Background/Objectives: Maximum aortic diameter remains central to abdominal aortic aneurysm (AAA) surveillance and decisions about repair, but it does not capture the full biological and mechanical state of the aneurysm wall. We explored diameter-associated transcriptomic patterns across human AAA datasets and compared responses associated with rupture and regional high wall stress. Methods: Six public human AAA transcriptomic datasets were reanalyzed using the same fixed 30-component biological-program panel while preserving the design and participant structure of each source study. Cross-dataset comparisons were performed on continuous custom-module effects. Uncertainty in the diameter comparison was assessed by resampling participants within both cohorts in 50,000 bootstrap replicates. Results: The diameter analyses showed a positive observed effect pattern (component Pearson r = 0.660; family Pearson r = 0.701), although no custom module reached nominal significance in both. The bootstrap median family correlation was lower (r = 0.306; 95% interval, −0.427 to 0.775), and the interval included zero. Rupture and high wall stress showed little overall molecular correlation (component r = 0.004; family r = 0.070), despite shared directions of selected hypoxia- and inflammation-related responses. Wall-layer, thrombus, and single-cell analyses revealed spatial and cellular heterogeneity. Conclusions: The observed diameter-associated molecular pattern remains exploratory rather than an established cross-dataset association. Aneurysm size, regional mechanical loading, and rupture appear to involve related but partly distinct aspects of AAA biology.