UP-REGULATION OF B-FGF RECEPTOR EXPRESSION AFTER CAROTID BYPASS

Basic fibroblast growth factor (b-FGF) appears to be an important posi tive modulator of the neointimal hyperplasia that occurs after prosthe tic vascular graft implantation through its effects on vascular myoint imal/smooth muscle cell migration and proliferation. The distribution and extent of b-FGF receptor (b-FGFR1) expression was compared using i mmunohistochemical techniques in normal porcine carotid arteries and a t various times up to 6 weeks following implantation of small caliber prosthetic vascular grafts. At the time of graft harvest, specimens we re infused with OCT medium at 100 mm Hg and rapidly frozen in liquid n itrogen. Transverse sections of the perianastomotic arterial tissues w ere labeled with primary mouse monoclonal antibody directed toward the extracellular domain of the receptor, followed by goat-anti mouse IgG and rabbit anti-goat IgG conjugated to horseradish peroxidase. The b- FGFR1-positive cells were identified by peroxidase activity within the Golgi complex of smooth muscle cells. Normal porcine carotid arteries showed no evidence of staining for b-FGFR1. However, at 6 weeks cells in the perianastomotic area clearly showed significant b-FGFR1 locali zation. Anti-muscle actin labeling confirmed these to be smooth muscle cells. The observed upregulation of b-FGFR1 expression supports the c oncept of positive feedback by cytokines as a contributing factor to t he hyperplastic response of smooth muscle cells after prosthetic vascu lar graft implantation. This finding further supports a potential stra tegy to specifically target activated smooth muscle cells through use of mitotoxin therapy. (C) 1995 Academic Press, Inc.