In vivo absence of synergism between fibroblast growth factor-2 and vascular endothelial growth factor

Fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF) are potent angiogenesis inducers in vivo and in vitro and may act in synergy. This possibility has been investigated by their simultaneous administration in the chick embryo chorioallantoic membrane (CAM) assay. Macroscopic and microscopic quantification of the angiogenic response 4 days after administration clearly demonstrated the absence of synergism. When FGF-2 or VEGF concentration was fixed at 0.25 microg/embryo, the simultaneous addition of increasing concentration (0.25, 0.50, 1.0 microg/embryo) of VEGF or FGF-2 did not stimulate a synergistic dose-dependent angiogenic response. In both conditions, the angiogenic response overlapped that induced by the two growth factors administered alone. It is suggested that exogenous administration of FGF-2 and VEGF in the CAM assay may induce an activation of endogenous angiogenic factors, such as FGF-2, and endogenous inhibitors of angiogenesis, such as nitric oxide, normally expressed in the CAM during the development of its vascular tree. Thus, in an in vivo system, evaluation of synergistic action between two cytokines and discrimination of their specific activity are more difficult than in an in vitro assay.