INFLAMMATION AND MATRIX METALLOPROTEINASES IN THE ENLARGING ABDOMINALAORTIC-ANEURYSM

The risk of rupture of an abdominal aortic aneurysm increases with aor tic diameter. To obtain insight into the pathological processes associ ated with the vascular remodeling that accompanies aortic dilatation, we compared the histological features and the activity of matrix metal loproteinases (MMPs) in biopsies from 21 small (4.0 to 5.5 cm in diame ter) and 45 larger abdominal aortic aneurysms. The histological featur e most clearly associated with enlarging aneurysm diameter was a highe r density of inflammatory cells in the adventitia, P=.018. This inflam mation was nonspecific, principally macrophages and B lymphocytes. Fib rosis of the adventitia provided compensatory thickening of the aortic wall as the aneurysm diameter increased. A combination of zymography and immunoblotting identified gelatinase A (MMP-2) as the principal me tallogelatinase in small aneurysms, whereas zymography indicated an in creasing activity of gelatinase B (MMP-9) in large aneurysms. Homogena tes prepared from both small and large aneurysms had similar total act ivity against, gelatin or type IV collagen. However, the concentration of gelatinase A, determined by immunoassay, was highest for small ane urysms: median concentrations, 385, 244, and 166 ng/mg protein for sma ll aneurysms, large aneurysms, and atherosclerotic aorta, respectively . Immunolocalization studies indicated that gelatinase A was concentra ted along fibrous tissue of both the acellular media and the atheroscl erotic plaque. The recruit ment of inflammatory cells into the adventi tia, with subsequent elaboration of metalloproteinases, including gela tinase B, may contribute to the rapid growth and rupture of larger ane urysms.