Jacob Theresa, Hingorani Anil, Ascher Enrico
Division of Vascular Surgery, Department of Surgery, Maimonides Medical Center, Brooklyn, NY, USA.
Vascular. 2005 Jan-Feb;13(1):34-42. doi: 10.1258/rsmvasc.13.1.34.
The objective of this study was to investigate the role of inflammation, programmed cell death, its molecular modulators, and proteolysis in the pathogenesis of iliac artery aneurysms (IAAs). Nineteen IAA specimens were obtained from patients undergoing elective surgical repair. All were males with ages ranging from 55 to 85 years (mean 73 years). Controls were iliac arteries (n=6) retrieved from surgical patients without aneurysmal disease. Standard histochemical techniques were used to assess elastic lamellae fragmentation and inflammatory infiltrate in aneurysmal and normal tissues Identification of different types of cells in the aneurysm wall and detection of death-pro molecules, Fas, p53, perforin, apoptosis-mediating bcl-2 family proteins, apoptotic death substrate, and poly(adenosine diphosphate-ribose) polymerase were performed immunohistochemically. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine triphosphate nick end-labeling (TUNEL) assay and caspase activity. Proteolytic activity was determined by 10% gelatin gel zymography. There is a conspicuous disruption and fragmentation of elastic lamellae in IAAs compared with normal arteries. Increased gelatinolytic activity was observed at 92, 72, and 67 kDa in the aneurysmal tissues. There was a significant loss of vascular smooth muscle cells (VSMCs) in the IAA walls compared with normal arteries (p < .02). Large numbers of inflammatory cells were observed in the IAA specimens (p = .01). Only aneurysmal arteries showed CD8+ T cells expressing death-promoting molecules. CD3+, CD8+, CD20+, CD30+, and CD68+ immunoreactive cells were significantly more prominent in the aneurysmal tissues than in the control arteries. There was a significant increase in the number of cells undergoing apoptosis in aneurysmal tissue than in the normal vessels (p < .02), as well as in the expression of bax, p53, CPP-32, and Fas. Apoptotic cells and proapoptotic molecules predominantly localized to the inflammatory infiltrate. VSMC apoptosis was significant in IAAs. The data confirm the architectural disruption of the IAA wall and illustrate an apparent biologic response involving inflammatory infiltrate, apoptosis, and signaling 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 favor IAA development.
