Temporal and Topographic Matrix Metalloproteinase Expression after Vascular Injury in Mice

H. R. Lijnen; F. Lupu; L. Moons; P. Carmeliet; D. Goulding; D. Collen

doi:10.1055/s-0037-1614573

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1999; 81(05): 799-807
DOI: 10.1055/s-0037-1614573

Rapid Communication

Schattauer GmbH

Temporal and Topographic Matrix Metalloproteinase Expression after Vascular Injury in Mice

Authors

H. R. Lijnen

¹From the Center for Molecular and Vascular Biology, University of Leuven, Belgium
F. Lupu

²Vascular Biology Laboratory, Thrombosis Research Institute, London, UK
L. Moons

³Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Leuven, Belgium
P. Carmeliet

³Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Leuven, Belgium
D. Goulding

²Vascular Biology Laboratory, Thrombosis Research Institute, London, UK
D. Collen

¹From the Center for Molecular and Vascular Biology, University of Leuven, Belgium

³Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Leuven, Belgium

Abstract

Summary

Temporal and topographic expression of matrix metalloproteinases (MMPs) after perivascular electric injury was studied in wild-type (WT) and urokinase-deficient (u-PA^-/-) mice. Neointima formation after injury of the femoral artery was significantly reduced in u-PA^-/- mice as compared to WT mice (area of 0.002 ± 0.0007 mm² versus 0.008 ± 0.002 mm² at 3 weeks after injury; p <0.001), associated with impaired cellular migration (nuclear cell counts of 44 ± 5 versus 82 ± 9 in cross-sectional areas; p <0.001).

Zymographic and/or microscopic analysis indicated that MMP expression gradually increased to reach a maximum at 1 to 2 weeks after vascular injury. In general, MMP levels were lower in u-PA^-/- than in WT mice. In non-injured arteries, MMP-2 (gelatinase A) and MMP-3 (stromelysin-1) were produced mainly by adventitial fibroblasts and/or non-contractile smooth muscle cells (SMC). One week after injury, MMP-2 and MMP-3 levels were enhanced due to an increased number and size of producing cells; 2 to 3 weeks after injury, MMP-2 and MMP-3 were produced also by some contractile SMC, which stained with α-actin antiserum. MMP-9 (gelatinase B), MMP-12 (metalloelastase) and MMP-13 (collagenase-3) were found in macrophages located mainly in the adventitia. Immunogold electron microscopic examination revealed that MMP-2 was located predominantly in association with the cell surface of fibroblasts or SMC, while MMP-9 and MMP-12 were located in well defined storage granules within macrophages. MMP-2, MMP-3 and MMP-13, but not MMP-9 or MMP-12, were also found extracellularly, associated with elastin-containing structures (MMP-2), with the basement membrane and occasionally with collagen fibres (MMP-3), or with proteoglycans, collagen and elastin (MMP-13).

The temporal and topographic expression pattern of MMPs after vascular injury, coinciding with smooth muscle cell migration and neointima formation, thus is compatible with a role in vascular remodeling.

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Referenzen

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