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.