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

• Published in: Circulation (New York, N.Y.) N.Y.), 2001-07, Vol.104 (3), p.304-309
• Main Authors: GOODALL, Stephen, CROWTHER, Mat, HEMINGWAY, David M, BELL, Peter R, THOMPSON, Matt M
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Aortic Aneurysm, Abdominal - enzymology; Aortic Aneurysm, Abdominal - pathology; Aortic Aneurysm, Abdominal - surgery; Biological and medical sciences; Blood and lymphatic vessels; Blotting, Northern; Cardiology. Vascular system; Cells, Cultured; Diseases of the aorta; Elastin - metabolism; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunohistochemistry; Male; Matrix Metalloproteinase 2 - genetics; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinases, Membrane-Associated; Medical sciences; Mesenteric Veins - cytology; Mesenteric Veins - enzymology; Metalloendopeptidases - genetics; Metalloendopeptidases - metabolism; Middle Aged; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - enzymology; RNA, Messenger - analysis; Tissue Inhibitor of Metalloproteinase-2 - genetics; Tissue Inhibitor of Metalloproteinase-2 - metabolism
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.104.3.304

Patients with abdominal aortic aneurysms (AAAs) exhibit arterial dilation and altered matrix composition throughout the vasculature. Matrix 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 primary etiological event in aneurysm genesis. The aim of this study was to investigate MMP-2 production in vascular tissue remote from the abdominal aorta. Inferior mesenteric vein (IMV) was harvested from patients undergoing aneurysm repair (n=21) or colectomy for diverticular disease (n=13, control). Matrix composition of the vessels was determined by stereological techniques. MMPs were extracted from tissue homogenates and quantified by gelatin zymography and ELISA. MMP-2, membrane type-1 MMP (MT1-MMP), and tissue inhibitor of metalloproteinases type 2 (TIMP-2) expression were determined by Northern analysis. SMCs were isolated from IMV, and the production and expression of MMP-2 and TIMP-2 in the SMC lines were quantified. Tissue homogenates and isolated inferior mesenteric SMCs from patients with aneurysms demonstrated significantly elevated MMP-2 levels, with no difference in TIMP-2 or MT1-MMP. These differences were a result of increased MMP-2 expression. Histological examination revealed fragmentation of elastin fibers within venous tissue obtained from patients with AAA and a significant depletion of the elastin within the media. In situ zymography localized elastolysis to medial SMCs. Patients with AAA have elevated MMP-2 levels in the vasculature remote from the aorta. This finding is due to increased MMP-2 expression from SMCs, a characteristic maintained in tissue culture. These data support both the systemic nature of aneurysmal disease and a primary role of MMP-2 in aneurysm formation.