Initial steps in the unifying theory of the pathogenesis of artery aneurysms

The objective of this study was to investigate the changes in histology and proteolysis and the role of apoptosis in the development of peripheral artery aneurysms.

Eighteen popliteal, 6 abdominal aortic, 10 iliac, 2 carotid, and 6 femoral artery aneurysm specimens were obtained from patients undergoing elective surgical repair. All were males with ages 48 to 93 (mean 71 years). Normal controls were obtained from patients matched for age, sex, and major risk factors. Vascular smooth muscle cells (VSMC), macrophages, T lymphocytes, and apoptosis-regulating molecules were detected immunohistochemically. Detection of apoptosis was by TUNEL assay. Proteolytic activity was determined by 10% gelatin gel zymography.

Paucity of VSMCs, increased amount of inflammatory infiltrate, and fragmentation of elastic lamellae were observed in aneurysmal tissues as compared to normal arteries (P < 0.02). There is increased gelatinolytic activity at 92, 84, 72, and 67 kDa in the aneurysmal tissues. There are fewer CD68+ macrophages and T cells in the media of controls than in the aneurysms (P = 0.01). Apoptosis is significantly high in aneurysm tissues (P < 0.01) and the degree of apoptosis was in the order AAA>FAA>PAA>IAA>CAA. There is increased expression of Bax, CPP-32, Fas, and p53 in PAA specimens as compared to normal popliteal arteries (P < 0.05).

These data confirm the apparent architectural disruption and loss of VSMCs that are hallmarks of aneurysm development, in peripheral artery aneurysms. Apoptosis and signaling molecules capable of initiating cell death may play a significant role in the pathogenesis of all aneurysms. Our data suggest a common etiology between the various types of aneurysms.