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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

Abstract

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
OAI identifier: oai:arts.units.it:11368/2899363
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