Stimulation of endothelial cells by doses of basic FGF-saporin that are lethal to smooth muscle cells

Basic fibroblast growth factor (FGF) receptors are up-regulated in proliferating (vs. quiescent) aortic smooth muscle cells, according to the results of recent studies. This up-regulation allows the ribosome inactivator saporin (if linked to basic FGF) to enter and kill proliferating, but not quiescent smooth muscle cells in vitro and in vivo. The authors now report that endothelial cells exhibit a different response. In 10% serum, FGF-SAP (0.1-1 nM) stimulates protein synthesis and cell division in subconfluent endothelial cells, but inhibits protein synthesis and cell division in subconfluent smooth muscle cells. Endothelial cells were inhibited at 10 nM FGF-SAP. A stimulatory response was seen in smooth muscle cells only at 0.1 nM FGF-SAP, and only after serum deprivation. Both cell types were resistant to FGF-SAP at high cell density. These responses correlated with FGF receptor density, which was sixfold higher in smooth muscle than endothelial cells and twice as high in serum-free smooth muscle cells as in serum-deprived smooth muscle cells. Moreover, a dose of FGFSAP that inhibited neointimal smooth muscle accumulation after balloon injury did not inhibit reendothelialization. Thus, there is a dose range at which FGF-SAP has unique properties that may make it useful in the treatment of vascular injury.