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MMP-12 has a role in abdominal aortic aneurysms in mice

By G. Matthew Longo, Steven J. Buda, Nicola Fiotti, Wanfen Xiong, Timothy Griener, Steven Shapiro and B. Timothy Baxter


Background. Matrix metalloproteinase (MMP)-12 levels are increased in the abdominal aortic\ud aneurysm (AAA), implicating this protease in AAA pathogenesis. The purpose of this study was to assess\ud the role of MMP-12 in aneurysm formation.\ud Methods. A murine aneurysm model was generated by periaortic application of 0.25 mol/L calcium\ud chloride (CaCl2) for 15 minutes. Aortic diameters were measured and compared before and 10 weeks\ud after aneurysm induction. Aortic diameter changes for wild type (WT) and MMP-12 knockout (MMP-\ud 12/) mice were determined. MMP-12 production in mouse aorta was analyzed by casein zymography.\ud MMP-2 and MMP-9 expressions were examined by gelatin zymography. Immunohistochemical study\ud was used to measure macrophage infiltration into the aorta.\ud Results. There is an increase of 63 ± 5% (mean ± SEM) in aortic diameters of WT mice after CaCl2\ud inductions, while MMP-12/ mice increased only 26 ± 14%. Connective tissue staining of aortic\ud sections from WT mice showed disruption and fragmentation of medial elastic fibers, while MMP-12/\ud mice showed only focal elastic lamellae breakdown. MMP-12 levels in WT mice were significantly\ud increased after CaCl2 treatment, whereas no MMP-12 was detected in MMP-12/ mice. There was no\ud difference in the MMP-2 and MMP-9 productions between WT and MMP-12/ mice. Immunohistochemical\ud analysis demonstrated that infiltrating macrophages in the aorta of MMP-12/ mice were\ud significantly less than WT controls.\ud Conclusions. MMP-12 deficiency attenuates aneurysm growth, possibly by decreasing macrophage\ud recruitment

Topics: Animals, Aortic Aneurysm, Abdominal, Calcium Chloride, Disease Models, Animal, Kinetics, Macrophages, Matrix Metalloproteinase 12, Metalloendopeptidases, Mice, Mice, Knockout, Surgery
Year: 2005
DOI identifier: 10.1016/j.surg.2004.12.004
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