Examination of the apoptotic pathway and proteolysis in the pathogenesis of popliteal artery aneurysms.
OBJECTIVE
to investigate the role of apoptosis, expression of death-promoting molecules and mediators of apoptosis in the development of popliteal artery aneurysms.


METHODS
ten popliteal artery aneurysm (PAA) specimens were obtained from patients undergoing elective surgical repair. Normal controls were popliteal arteries obtained from patients without PAA undergoing infrainguinal bypass surgery (n=8). Standard histochemistry techniques were used to assess elastic lamellae fragmentation and inflammatory infiltrate in PAA. Vascular smooth muscle cells (VSMC), macrophages, T lymphocytes, death-promoting molecules, CPP-32, Fas, p53, perforin, apoptosis-mediating Bcl-2 family proteins and apoptotic death substrate, poly(ADP-ribose) polymerase (PARP) were detected immunohistochemically. Detection of apoptosis was by TUNEL assay. Proteolytic activity was determined by 10% gelatin gel zymography.


RESULTS
there is a conspicuous disruption and fragmentation of elastic lamellae in PAA as compared to normal arteries. Increased gelatinolytic activity was observed at 92, 84, 72 and 67 kDa in PAA tissues. There is a significant decrease of VSMCs in the PAA walls (p=0.02). The control arteries had 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 increased 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 infiltrate, apoptosis and signalling molecules capable of initiating cell death. In addition to compromising the mechanical integrity of the vessel wall, VSMC loss may contribute to imbalance in the protein profile, accelerating extracellular matrix degradation that could favour PAA development.
Jacob
T
T
Division of Vascular Surgery, Maimonides Medical Center, Brooklyn, NY 11219, USA.
Hingorani
A
A
Ascher
E
E
D000368:Aged; D000369:Aged, 80 and over; D000783:Aneurysm / Q000503:physiopathology*; D017209:Apoptosis; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D011150:Popliteal Artery / Q000473:pathology