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

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