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

Area of Science:

• Vascular Biology
• Biomedical Engineering
• Pathophysiology

Background:

• Abdominal aortic aneurysm (AAA) is a degenerative vascular disease.
• AAA involves significant remodeling of the aortic wall, leading to mechanical failure.

Purpose of the Study:

• To comprehensively analyze AAA pathophysiology using a multimodal approach.
• To compare aneurysmal abdominal aortic tissue with subject-matched non-aneurysmal thoracic aortic tissue.
• To elucidate disease-specific mechanisms by eliminating inter-subject variability.

Main Methods:

• Integrated micro-CT imaging, histology, matrix metalloproteinase (MMP) analysis, and mechanical testing.
• Compared aneurysmal abdominal aortic (AAA) tissue with non-aneurysmal thoracic aortic tissue from the same donor.
• Assessed elastin degradation, smooth muscle cell content, fibrosis, calcification, MMP activity, and tissue mechanics.

Main Results:

• AAA segments showed severe elastin degradation, smooth muscle cell loss, fibrosis, and increased calcification.
• AAA tissue exhibited elevated total MMP activity and increased MMP-9 activity.
• AAA tissues were significantly stiffer and less extensible than control thoracic tissues.

Conclusions:

• Elastin degradation, proteolytic enzyme activity, and fibrotic remodeling are interconnected in AAA mechanical failure.
• An intra-subject study design is valuable for understanding disease-specific mechanisms in AAA.
• Findings highlight key pathological features contributing to aortic wall failure in AAA disease.