Localization and effects of hepatocyte growth factor on smooth muscle cells during neointimal formation after balloon denudation.
The migration and proliferation of smooth muscle cells (SMCs) may play a key role in tissue remodeling after arterial wall injury. We investigated the localization and effects of hepatocyte growth factor (HGF) in rabbit carotid arteries after balloon denudation. Immunoreactivity for HGF and the c-Met receptor was clearly observed in neointimal SMCs. The immunoreactivity was not restricted to proliferating cells but was seen even in non-dividing cells in the basal layer of the neointima 4 and 6 weeks after balloon denudation. The distribution of platelet-derived growth factor (PDGF)-positive cells paralleled that of proliferating SMCs. The SMCs in the basal layer of the neointima at 4 and 6 weeks were positive for matrix metalloproteinase (MMP)-2 and membrane type 1-MMP which can activate the proform of MMP-2. HGF significantly stimulated the migration but not proliferation of cultured SMCs. Our results suggest that HGF and PDGF act in coordination to promote the proliferation and migration of SMCs in the earlier phases of neointimal formation and that HGF as well as MMP-2 contribute to the later stages by facilitating the migration but not replication of SMCs.
Aoyagi
M
M
Department of Neurosurgery, School of Medicine, Tokyo Medical and Dental University, Japan.
Yamamoto
S
S
Azuma
H
H
Yamamoto
M
M
Tamaki
M
M
Niimi
Y
Y
Hirakawa
K
K
Yamamoto
K
K
D000818:Animals; D002339:Carotid Arteries / Q000737:chemistry; D020212:Carotid Artery Injuries; D002404:Catheterization; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism; D018093:Gelatinases / Q000032:analysis; D017228:Hepatocyte Growth Factor / Q000032:analysis* / Q000494:pharmacology; D008297:Male; D020778:Matrix Metalloproteinase 2; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000032:analysis; D009131:Muscle, Smooth, Vascular / Q000737:chemistry* / Q000166:cytology; D010982:Platelet-Derived Growth Factor / Q000032:analysis; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis; D011817:Rabbits
D010982:Platelet-Derived Growth Factor; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D018093:Gelatinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2