Immunolocalization of matrix metalloproteinases in rabbit carotid arteries after balloon denudation

Extracellular matrix-degrading enzymes may play a key role in vascular remodeling after arterial wall injury. We investigated the immunolocalization of matrix metalloproteinases (MMPs) in rabbit carotid arteries after balloon denudation. Positive immunostaining for MMP-1, -2, -3, and -9 appeared through the neointima 1 week after balloon denudation. The localization of immunopositive smooth muscle cells (SMCs) for MMP-1, -3, and -9, particularly for MMP-9, was almost similar to that of replicative SMCs and became confined to the luminal surface layer of the neointima at later time periods. However, MMP-2-positive SMCs appeared also in the basal layer of the neointima at 2 weeks, increased at 4 weeks, and then totally occupied the neointima at 6 weeks. The MMP-2-positive SMCs in the basal layer of the neointima at 4 and 6 weeks were negative for proliferation-associated antigens and were surrounded by extracellular matrix proteins. Our results suggest that all MMPs act in coordination to promote replication and migration of SMCs in the earlier phases of neointimal formation and that MMP-2 independently contributes to the later stages by facilitating the migration but not replication of SMCs from the media to the intima.