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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:2863.)
© 1999 American Heart Association, Inc.

Vascular Biology

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

H. Roger Lijnen; Berthe Van Hoef; Ingrid Vanlinthout; Maria Verstreken; Marie-Christine Rio; Désiré Collen

From the Center for Molecular and Vascular Biology (H.R.L., B.V.H., I.V., M.V., D.C.), University of Leuven, Leuven, Belgium; and CNRS-INSERM-ULP (M.-C.R.), Illkirch, France.

Correspondence to H. R. Lijnen, Center for Molecular and Vascular Biology, University of Leuven, Campus Gasthuisberg, O & N, Herestraat 49, B-3000 Leuven, Belgium. E-mail: roger.lijnen{at}med.kuleuven.ac.be

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 -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.

Key Words: neointima • restenosis • transgenic mice • stromelysin-3

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