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

This study used a multimodal intra-subject design to characterize abdominal aortic aneurysm pathophysiology by comparing aneurysmal abdominal aortic tissue with non-aneurysmal thoracic aortic tissue from the same deceased human donors. The approach reduced inter-subject variability by using each donor as their own control. Whole aortas from two female donors with intact AAAs were analyzed using micro-CT imaging, histology, immunohistochemistry, MMP activity assays, gelatin zymography, and planar biaxial mechanical testing. Micro-CT showed extensive calcification in the aneurysmal segments, including sheet-like and nodular deposits. Histological stains revealed severe elastin degradation, smooth muscle cell loss, glycosaminoglycan accumulation, dense collagen deposition, and circumferentially heterogeneous fibrosis in the AAA walls compared with more organized thoracic aortic controls. MMP analysis showed elevated total MMP activity in AAA tissue, with zymography indicating increased MMP-9 activity and reduced MMP-2 activity in late-stage aneurysmal tissue. BioTester biaxial testing showed that AAA tissues were markedly stiffer and less extensible than subject-matched thoracic aorta samples. Overall, the study linked elastin loss, proteolytic activity, fibrosis, calcification, and altered biaxial mechanics as connected features of advanced aneurysmal degeneration.