Death of smooth muscle cells and expression of mediators of apoptosis by Tlymphocytes in human abdominal aortic aneurysms

Background-Thinning of the tunica media and rarefaction of smooth muscle ce lls (SMCs) characterize aneurysmal aortas. Apoptosis determines the cellula rity and morphogenesis of tissue. Macrophages and T lymphocytes infiltrate the wall of abdominal aortic aneurysms (AAAs) and produce death-promoting p roteins (perforin, Fas, and Fast). This study investigated whether apoptosi s 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 r epair (n=20), Anti-alpha-actin immunostaining showed a reduced number of SM Cs in AAAs. In situ terminal transferase-mediated dUTP nick end-labeling (T UNEL) showed higher levels of DNA fragmentation in AAAs than in controls (n =5). The AAA walls contained more cells bearing markers of apoptosis than n ormal aorta (P<0.05, Student's t test). Double immunostaining identified SM Cs and macrophages as the principal cell types displaying fragmented DNA. I mmunohistochemistry 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-re ceptor interaction. Double immunostaining also identified SMCs that express ed Fas, Immunoblotting confirmed the presence and, in the case of Fas, acti vation 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 red uction of cellularity and to the impaired repair and maintenance of the art erial extracellular matrix in AAAs. Macrophages and T lymphocytes infiltrat e the wall of AAAs, where they can produce cytotoxic mediators such as cyto kines, 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.