Examination of the apoptotic pathway and proteolysis in the pathogenesis of popliteal artery aneurysms

Objectives: to investigate the role of apoptosis, expression of death-promo ting molecules and mediators of apoptosis in the development of popliteal a rtery aneurysms. Methods: ten popliteal artery aneurysm (PAA) specimens were obtained from p atients undergoing elective surgical repair. Normal controls were popliteal arteries obtained from patients without PAA undergoing infrainguinal bypas s surgery (n = 8). Standard histochemistry techniques were used to assess e lastic lamellae fragmentation and inflammatory infiltrate in PAA. Vascular smooth muscle cells (VSMC), macrophages, T lymphocytes, death-promoting mol ecules, CPP-32, Fas, p53, perforin, apoptosis-mediating Bcl-2 family protei ns and apoptotic death substrate, poly(ADP-ribose) polymerase (PARP) were d etected immunohistochemically. Detection of apoptosis was by TUNEL assay. P roteolytic activity was determined by 10% gelatin gel zymography. Results: there is a conspicuous disruption and fragmentation of elastic lam ellae in PAA as compared to normal arteries. Increased gelatinolytic activi ty was observed at 92, 84, 72 and 67 kDa in PAA tissues. There is a signifi cant decrease of VSMCs in the PAA walls (p = 0.02). The control arteries ha d fewer CD68+ macrophages and CD3+ T cells in their media (p < 0.01). There was a significant increase in the number of cells undergoing apoptosis in aneurysmal tissue than in the normal vessels, (p < 0.02) as well as an incr eased expression of Bax, CPP- 32, Fas, p53 and perforin. Conclusions: the data confirm the architectural disruption of the PAA wall and illustrate an apparent biological response involving inflammatory infil trate, apoptosis and signalling molecules capable of initiating cell death. In addition to compromising the mechanical integrity of the vessel wall, V SMC loss may contribute to imbalance in the protein profile, accelerating e xtracellular matrix degradation that could favour PAA development.