Matrix Metalloproteinase-2 Production and Its Binding to the Matrix Are Increased in Abdominal Aortic Aneurysms

From the Departments of Surgery (V.D., R.P., L.B.-R., B.T.B.) and of Pathology and Microbiology (V.D., Y.P., A.G., B.T.B.), University of Nebraska Medical Center, Omaha, and the Department of Biochemistry and Molecular Biology (Y.I., H.N.), University of Kansas Medical Center, Kansas City.

Correspondence to B. Timothy Baxter, MD, University of Nebraska Medical Center, 600 S 42nd St, Omaha, NE 68198-3280. E-mail btbaxter{at}mail.unmc.edu

Abstract—Degradation of the elastic media is a hallmark of abdominal aortic aneurysms (AAAs). We examined the expression of 2 elastolytic matrix metalloproteinases (MMPs), MMP-2 and MMP-9, in AAA aortic tissues compared with those from atherosclerotic occlusive disease (AOD) and nondiseased control tissues. Quantitative competitive reverse transcription–polymerase chain reaction and gelatin zymography showed increased MMP-9 mRNA and protein in both AAA and AOD tissues compared with those in control tissue, but there was no significant difference between AAA and AOD. In contrast, MMP-2 mRNA and protein levels were significantly higher in AAA than in AOD or control tissues. Sequential extraction of the MMPs from the aortic tissue with a physiological salt solution, 2% dimethylsulfoxide (DMSO), and 10 mol/L urea showed that large amounts of MMP-2 and MMP-9 were bound to the matrix. The most conspicuous finding was that the levels of MMP-2 were significantly elevated in the DMSO fraction in AAA tissues compared with AOD and control tissues. In addition, a large portion of MMP-2 found in the DMSO and urea fractions was in the active 62-kDa form, indicating that the precursor of MMP-2 in AAA is largely activated locally and binds to the tissue matrix tightly. By immunolocalization, MMP-9 was found to be primarily produced by macrophages and MMP-2 by mesenchymal cells. The production of MMP-2 was prominent when mesenchymal cells were surrounded by inflammatory cells, suggesting paracrine modulation of MMP-2 expression in AAAs. These observations emphasize that MMP-2 participates in the progression of AAAs by degrading aortic tissue matrix components.

Key Words: abdominal aortic aneurysms • matrix metalloproteinases • smooth muscle cells • macrophages • lymphocytes

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