FIBROBLAST GROWTH-FACTOR RECEPTOR-1 EXPRESSION IS ASSOCIATED WITH NEOINTIMAL FORMATION IN-VITRO

Neointimal formation was studied in a porcine aortic organ culture mod el that exhibits intimal smooth muscle cell accumulation after a brief time in culture. This in vitro model is dependent upon an intact endo thelium, as removal of the endothelium at the time of harvesting resul ts in the failure to develop a neointima, We previously shouted that c onditioned media from intact cultures induce neointimal formation in d enuded aortic explants, and we speculated that basic fibroblast growth factor was the endothelial-derived-factor in conditioned media promot ing neointimal formation. However, the concentration of basic fibrobla st growth factor in conditioned media from both intact and denuded exp lants, measured by an enzyme-linked immunosorbent assay, was not signi ficantly different and, in fact, steadily decreased over the first 7 d ays of culture, Furthermore, the amount and intensity of immunoreactiv e basic fibroblast growth factor in tissue sections, also similar in b oth groups, decreased over the same time course, Nonetheless, exogenou s basic fibroblast growth factor (1 ng/ml) induced neointimal formatio n in intact explants but was unable to do so in denuded explants. West ern blot analysis of intimal lysates prepared from both intact and den uded explants showed a the-dependent increase in fibroblast growth fac tor receptor-1 expression over the first 7 days of culture, with highe r levels seen in intimal lysates from intact explants at each time poi nt examined. Immunoreactive fibroblast growth factor receptor-1 was de tected in both endothelial cells and intimal smooth muscle cells of in tact explant sections, These data indicate that, in the presence of tb e endothelium, neointimal formation may in part be mediated by upregul ation of fibroblast growth factor receptor-1 in the intimal cells of p orcine aortic explants.