DECREASED VASCULAR SMOOTH-MUSCLE CELL-DENSITY IN MEDIAL DEGENERATION OF HUMAN ABDOMINAL AORTIC-ANEURYSMS

Abdominal aortic aneurysms (AAAs) are characterized by structural dete rioration of the aortic wall leading to progressive aortic dilatation and eventual rupture. The histopathological changes in AAAs are partic ularly evident within the elastic media, which is normally dominated b y vascular smooth muscle cells (SMCs). To determine whether a decrease in vascular SMCs contributes to medial degeneration, we measured SMC density in 21 normal and pathological human abdominal aortic tissue sp ecimens using immunohistochemistry for alpha-SMC actin and direct cell counts (medial SMCs per high-power field (HPF)). Medial SMC density w as not significantly different between normal aorta (n = 5; 199.5 +/- 14.9 SMCs/HPF) and atherosclerotic occlusive disease (n = 6; 176.4 +/- 13.9 SMCs/HPF), but it was reduced by 74% in AAA (n = 10; 50.9 +/- 6. 1 SMCs/HPF; P < 0.01 versus normal aorta). Light and electron microsco py revealed no evidence of overt cellular necrosis, but SMCs in AAAs e xhibited ultrastructural changes consistent with apoptosis. Using in s itu end-labeling (ISEL) of fragmented DNA to detect apoptotic cells, u p to 30% of aortic wall cells were ISEL positive in AAAs. By double-la beling techniques, many of these cells were alpha-actin-positive SMCs distributed throughout the degenerative media. In contrast, ISEL-posit ive cells were observed only within the intimal plaque in atherosclero tic occlusive disease. The amount of p53 protein detected by immunoblo tting tons increased nearly fourfold in AAA compared with normal aorta and atherosclerotic occlusive disease (P < 0.01), and immunoreactive p53 was localized to lymphocytes and residual SMCs in the aneurysm wal l, Using reverse transcription polymerase chain reaction assays a subs tantial amount of p53 mRNA expression was observed in AAAs, These resu lts demonstrate that medial SMC density is significantly decreased in human AAA tissues associated with evidence of SMC apoptosis and increa sed production of p53, a potential mediator of cell cycle arrest and p rogrammed cell death, Given the role that SMCs normally play in mainta ining medial architecture and in arterial wall matrix remodeling, the induction of SMC apoptosis likely mates an important contribution to t he evolution of aneurysm degeneration.