A 60-year-old man with poorly controlled hypertension has an incidental finding of a 5.5 cm infrarenal abdominal aortic aneurysm (AAA). Pathological examination of a resected specimen shows thinned and disrupted elastic laminae, smooth muscle cell depletion, and atherosclerosis, with inflammatory infiltration and neovascularization of the adventitia. Which enzymatic mechanism is primarily responsible for elastic lamina destruction in AAA?

• A Cathepsin K-mediated collagen degradation in macrophages preferentially destroys type IV collagen of the basement membrane, secondarily destabilizing the elastic laminae
• B Tissue factor pathway inhibitor (TFPI) deficiency in AAA wall activates thrombin-mediated fibronectin cleavage, destabilizing the extracellular matrix indirectly
• C Matrix metalloproteinases (MMP-2, MMP-9 — gelatinases) and serine proteases (plasmin, elastase from neutrophils/macrophages) proteolytically degrade elastin and collagen in the media; MMP-9 from adventitial macrophages/neutrophils is the primary elastolytic enzyme ✓
• D Complement C5b-9 (MAC) deposition on elastic laminae is the primary mechanism, directly lysing the non-cellular elastin fibers via osmotic pressure

Explanation

AAA pathogenesis involves medial degeneration through proteolytic degradation of the extracellular matrix, particularly elastin and collagen. Matrix metalloproteinases — especially MMP-2 (gelatinase A) and MMP-9 (gelatinase B, the most abundant elastolytic enzyme in AAA tissue) — are produced predominantly by macrophages, neutrophils, and smooth muscle cells in the adventitia and media. Neutrophil-derived serine elastases (neutrophil elastase) and cathepsins (K, L, S) also contribute. The balance between MMPs and their inhibitors (TIMPs, tissue inhibitors of metalloproteinases) is shifted toward proteolysis in AAA. MMP-9 levels in AAA wall correlate with aneurysm expansion rate, making it a therapeutic target (doxycycline as an MMP inhibitor has been investigated). Cathepsin K primarily degrades collagen I/II; MAC does not lyse extracellular matrix proteins.

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

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