PDGF LIGAND AND RECEPTOR GENE-EXPRESSION DURING REPAIR OF ARTERIAL INJURY

Smooth muscle cells (SMC) in rat carotid artery leave the quiescent state and proliferate after balloon catheter injury, but the signals for mitogenesis are not known. In this study, the possibility that cells within damaged arteries produce a growth factor that could act locally to stimulate SMC replication and repair was examined. We found that the genes for PDGF-A and -B (ligand) and PDGF receptor (α and β subunits) were expressed in normal and injured carotid arteries and were independently regulated during repair of carotid injury. Two phases of PDGF ligand and receptor gene expression were observed: (a) In the early stage, a large decrease in PDGF β-receptor mRNA levels preceded 10- to 12-fold increases in PDGF-A transcript abundance in the first 6 h after wounding. No change in PDGF α-receptor or PDGF-B gene expression was found at these times, (b) In the chronic phase, 2 wk after injury, neointimal tissue had lower levels of PDGF α-receptor mRNA (threefold) and higher levels of PDGF β-receptor mRNA (three- to fivefold) than did restored media. Moreover, in situ hybridization studies identified a subpopulation of neointimal SMC localized at or near the luminal surface with a different pattern of gene expression than the underlying carotid SMC. Luminal SMC were strongly positive for PDGF-A and PDGF β-receptor transcripts, while showing little or no hybridization for PDGF-B or PDGF α-receptor. Immunohistochemical studies showed strongly positive staining for PDGF-A in SMC along the luminal surface. These data show that changes in PDGF ligand and receptor expression occur at specific times and locations in injured carotid artery and suggest that these changes may play a role in regulating arterial wound repair.