Multimodal intra-subject characterization of abdominal aortic aneurysm pathophysiology: a case study

Abdominal aortic aneurysm (AAA) is a degenerative vascular disease characterized by significant remodeling of the aortic wall. This study presents a comprehensive, multimodal analysis of AAA pathophysiology by comparing aneurysmal abdominal aortic tissue with non-aneurysmal thoracic aortic tissue of the same deceased human donor (N = 2), eliminating inter-subject differences. The multimodal approach integrated micro-CT imaging, transverse section histology, matrix metalloproteinase (MMP) analysis, and planar biaxial mechanical testing. Compared to the subject-matched thoracic controls, the AAA segments exhibited severe and heterogeneous degradation of the elastic network, profound loss of smooth muscle cells, extensive fibrosis, and a significant increase in calcification volume. Biochemically, AAA tissue showed elevated total MMP activity. In parallel, gelatin zymography tests validated an increase in MMP-9 activity in the diseased segments. Moreover, AAA tissues were substantially stiffer and less extensible than the corresponding healthy aortic tissue. These data, taken together, underscore the interconnected roles of elastin degradation, proteolytic enzyme activity, and fibrotic remodeling in the mechanical failure of the aortic wall, while highlighting the value of an intra-subject study design for elucidating disease-specific mechanisms.