Death of smooth muscle cells and expression of mediators of apoptosis by T lymphocytes in human abdominal aortic aneurysms.

BACKGROUND: Thinning of the tunica media and rarefaction of smooth muscle cells (SMCs) characterize aneurysmal aortas. Apoptosis determines the cellularity and morphogenesis of tissue. Macrophages and T lymphocytes infiltrate the wall of abdominal aortic aneurysms (AAAs) and produce death-promoting proteins (perforin, Fas, and FasL). This study investigated whether apoptosis occurs in association with the expression of these proteins. METHODS AND RESULTS: We examined signs of apoptosis and expression of death-promoting mediators in segments of AAAs from patients undergoing elective repair (n=20). Anti-alpha-actin immunostaining showed a reduced number of SMCs in AAAs. In situ terminal transferase-mediated dUTP nick end-labeling (TUNEL) showed higher levels of DNA fragmentation in AAAs than in controls (n=5). The AAA walls contained more cells bearing markers of apoptosis than normal aorta (P<0.05, Student's t test). Double immunostaining identified SMCs and macrophages as the principal cell types displaying fragmented DNA. Immunohistochemistry revealed that AAAs but not normal aorta contained CD4(+) and CD8(+) T cells that expressed well-characterized cytotoxic mediators: perforin, which produces membrane damage, and Fas, which acts by ligand-receptor interaction. Double immunostaining also identified SMCs that expressed Fas. Immunoblotting confirmed the presence and, in the case of Fas, activation of these proteins in aneurysmal tissue. CONCLUSIONS: Many medial SMCs in AAAs bear markers of apoptosis and signals capable of initiating cell death. Apoptotic death may contribute to the reduction of cellularity and to the impaired repair and maintenance of the arterial extracellular matrix in AAAs. Macrophages and T lymphocytes infiltrate the wall of AAAs, where they can produce cytotoxic mediators such as cytokines, perforin, and Fas/FasL. These death-promoting products of activated immune cells may contribute to elimination of SMCs, a source of elastin and collagen, during the pathogenesis of AAAs.

Superficial femoral artery stenoses: characteristics of progressing lesions.

PURPOSE: The purpose of this study was to assess the effect of superficial femoral artery (SFA) stenosis morphologic characteristics and lesion location on the rate of atherosclerotic disease progression. METHODS: We identified 19 patients who required arteriography for treatment of critical leg ischemia and who had previously undergone arteriography of that leg when minimal or no symptoms were present. These initial incidental arteriographic evaluations were performed during evaluation of arterial disease in another vascular bed from 4 to 81 months (mean, 32 months) previously. Distinct SFA stenoses or occlusion on the final arteriogram (n = 98) were characterized by their location, length, stenosis severity, and morphologic appearance on the initial arteriogram. The contribution of patient-specific risk factors to disease progression was also assessed. RESULTS: Stenosis progression occurred independently among multiple lesions within the same patient (negligible intraclass correlation coefficient, r = 0.06). Lesions in the adductor canal region were more likely to occlude than lesions elsewhere in the SFA (adjusted odds ratio = 10.7; p = 0.03). Severity of initial lesion stenosis also was predictive of occlusion (adjusted odds ratio = 1.8; p = 0.04). However, most progressing lesions (93%) actually arose in areas of initially mild disease (stenoses < 50%) despite more severe initial lesions elsewhere. Increasing age (p = 0.023) and previous contralateral leg bypass (p = 0.036) were also associated with increasing rates of lesion progression. Smooth-asymmetric lesions progressed 11% more slowly than other lesion types (p = 0.003). CONCLUSIONS: Our analysis of atherosclerotic SFA lesion progression in patients with critical ischemia shows that initial stenosis severity was associated with higher occlusion rates and that smooth-asymmetric lesions progressed more slowly than lesions with other morphologic characteristics. Severe stenoses usually arose from minimally diseased regions and progressed more rapidly than preexisting, more highly stenotic lesions. Most SFA occlusions resulted from disease progression in the adductor canal region whether or not antecedent lesions were seen on arteriography and whether or not more severe stenoses were initially present elsewhere. Increased age and history of previous contralateral bypass were patient-specific predictors of lesion progression.