A 65-year-old hypertensive man is found to have a 5.5 cm infrarenal aortic aneurysm on CT. Pathology of resected aortic wall shows transmural destruction of the media with loss of smooth muscle cells and elastic lamellae, adventitial lymphoplasmacytic infiltration, and abundant matrix metalloproteinase (MMP) expression. What is the primary pathogenic mechanism responsible for medial degeneration in abdominal aortic aneurysm (AAA)?

• A Cystic medial necrosis — mucoid pools and smooth muscle cell loss from MYH11/FBN1/ACTA2 genetic defects
• B Intramural haematoma from vasa vasorum rupture leading to medial necrosis and outward dissection
• C Type III collagen (COL3A1) deficiency reducing tensile strength of the aortic wall
• D Proteolytic degradation of the aortic ECM by MMP-2 and MMP-9 (gelatinases), predominantly derived from macrophages and neutrophils in the adventitia/media, driven by TIMP-1/2 imbalance and pro-inflammatory cytokines (IL-6, TNF-alpha, IFN-gamma) ✓

Explanation

Abdominal aortic aneurysm pathogenesis is primarily driven by proteolysis of elastic and collagenous ECM components. MMP-2 (gelatinase A) and MMP-9 (gelatinase B), along with MMP-1, MMP-3, MMP-12 (elastase), are secreted by macrophages/neutrophils in the chronic adventitial and medial inflammatory infiltrate. These MMPs degrade elastin and collagen in an environment where TIMP-1 (tissue inhibitor of metalloproteinase) is insufficient to counterbalance MMP activity. Pro-inflammatory cytokines (IL-1beta, IL-6, TNF-alpha, IFN-gamma) upregulate MMP expression. Genetic predisposition (family history) and risk factors (smoking, hypertension) compound this. Cystic medial necrosis characterises thoracic aortic aneurysm in Marfan/Loeys-Dietz syndromes. COL3A1 defects cause vascular Ehlers-Danlos syndrome.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

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