Accelerated Neointima Formation After Vascular Injury in Mice With Stromelysin-3 (MMP-11) Gene Inactivation

Abstract —The hypothesis that stromelysin-3 (MMP-11), a unique member of the matrix metalloproteinase (MMP) family, plays a role in neointima formation was tested with the use of a vascular injury model in wild-type (MMP-11+/+) and MMP-11–deficient (MMP-11−/−) mice. Neointima formation 2 to 3 weeks after electric injury of the femoral artery was significantly enhanced in MMP-11−/− as compared with MMP-11+/+ mice, in both mice of a pure 129SV genetic background (0.014 versus 0.0010 mm2 at 2 weeks, P <0.001) and those of a 50/50 mixed 129SV/BL6 background (0.030 versus 0.013 mm2 at 3 weeks, P <0.05). The medial areas were comparable, resulting in intima/media ratios that were significantly increased in MMP-11−/− as compared with MMP-11+/+ arteries, in mice of both the 129SV (1.0 versus 0.18, P <0.001) and mixed (1.5 versus 0.70, P <0.05) backgrounds. Nuclear cell counts in cross-sectional areas of the intima of the injured region were higher in arteries from MMP-11−/− mice than in those from MMP-11+/+ mice (210 versus 48, P <0.001, in pure 129SV mice and 290 versus 150, P <0.01, in mice of the mixed genetic background). Immunocytochemical analysis revealed that α-actin–positive and CD45-positive cells were more abundant in intimal sections of MMP-11−/− mice. Degradation of the internal elastic lamina was more extensive in arteries of MMP-11−/− mice than in those of MMP-11+/+ mice (39% versus 6.8% at 3 weeks, P <0.005). The mechanisms by which MMP-11 could impair elastin degradation and cellular migration in this model remain, however, unknown.