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 ke y role in tissue remodeling after arterial wall injury. We investigated the localization and effects of hepatocyte growth factor (HGF) in rabbit carot id arteries after balloon denudation. Immunoreactivity for HGF and the c-Me t receptor was clearly observed in neointimal SMCs. The immunoreactivity wa s not restricted to proliferating cells but was seen even in non-dividing c ells in the basal layer of the neointima 4 and 6 weeks after balloon denuda tion. The distribution of platelet-derived growth factor (PDGF)positive cel ls paralleled that of proliferating SMCs. The SMCs in the basal layer of th e neointima at 4 and 6 weeks were positive for matrix metalloproteinase (MM P)-2 and membrane type 1-MMP which can activate the preform of MMP-2. HGF s ignificantly stimulated the migration but not proliferation of cultured SMC s. Our results suggest that HGF and PDGF act in coordination to promote the proliferation and migration of SMCs in the earlier phases of neointimal fo rmation and that HGF as well as MMP-2 contribute to the later stages by fac ilitating the migration but not replication of SMCs.