Ubiquitous elevation of matrix metalloproteinase-2 expression in the vasculature of patients with abdominal aneurysms

Background - Patients with abdominal aortic aneurysms (AAAs) exhibit arteri al dilation and altered matrix composition throughout the vasculature. Matr ix metalloproteinase-2 (MMP-2) is the dominant elastase in small AAAs, and overexpression of MMP-2 in vascular smooth muscle cells (SMCs) may be a pri mary etiological event in aneurysm genesis. The aim of this study was to in vestigate MMP-2 production in vascular tissue remote from the abdominal aor ta. Methods and Results - Inferior mesenteric vein (IMV) was harvested from pat ients undergoing aneurysm repair (n=21) or colectomy for diverticular disea se (n=13, control). Matrix composition of the vessels was determined by ste reological techniques. MMPs were extracted from tissue homogenates and quan tified by gelatin zymography and ELISA, MMP-2, membrane type-1 MMP (MT1-MMP ), and tissue inhibitor of metalloproteinases type 2 (TIMP-2) expression we re determined by Northern analysis. SMCs were isolated from IMV, and the pr oduction and expression of MMP-2 and TIMP-2 in the SMC lines were quantifie d. Tissue homogenates and isolated inferior mesenteric SMCs from patients w ith aneurysms demonstrated significantly elevated MMP-2 levels, with no dif ference in TIMP-2 or MT1-MMP. These differences were a result of increased MMP-2 expression. Histological examination revealed fragmentation of elasti n fibers within venous tissue obtained from patients with AAA and a signifi cant depletion of the elastin within the media. In situ zymography localize d elastolysis to medial SMCs. Conclusions - Patients with AAA have elevated MMP-2 levels in the vasculatu re remote from the aorta. This finding is due to increased MMP-2 expression from SMCs, a characteristic maintained in tissue culture. These data suppo rt both the systemic nature of aneurysmal disease and a primary role of MMP -2 in aneurysm formation.