Differential expression of YAMA/CPP-32 by T lymphocytes in popliteal artery aneurysm

We have previously demonstrated that programmed cell death, proteolytic activity, and inflammatory infiltrate in the aneurysmal wall may have a role in the pathogenesis of popliteal artery aneurysms (PAA). This investigation examines the expression of a cell death-promoting molecule, a cysteine protease, YAMA/CPP-32 in a series of PAA specimens.

Twenty PAA specimens were obtained from patients undergoing elective surgical repair. Normal controls were popliteal arteries obtained from patients without PAA who were undergoing infrainguinal bypass surgery (n = 8). Standard histochemistry techniques were used to assess inflammatory infiltrates in PAA. Expression of apoptosis-promoting molecule, CPP-32, vascular smooth muscle cells (VSMC), macrophages, and T lymphocytes was detected by immunohistochemistry.

There is a conspicuous disruption and fragmentation of elastic lamellae and increased inflammatory infiltrate in the PAA as compared with normal arteries. As compared with normal popliteal artery tissues, the PAA demonstrated large number of cells immunopositive for CPP-32 (60.45 +/- 4.25% P < 0.05). This study revealed significantly increased expression of CPP-32 in the T-cell population of the PAA as compared with the other cells (P < 0.01). Dual immunolabeling and investigation of serial sections demonstrated that co-expression of CPP-32 was maximum in the CD8+ subset (37 +/- 3.3% of the total CPP-32 immunoreactive cells identified).

The data emphasize that the inflammatory infiltrate in the PAA walls has a significant role in the pathogenesis of this vascular disorder. Cells expressing death-promoting molecules are present in large numbers and are predominantly T lymphocytes in PAA. In addition to compromising the mechanical integrity of the vessel wall, apoptosis in the inflammatory infiltrate may contribute to the production of cytokines, activation of other signaling molecules such as stress proteins that could eventually favor PAA development.