Basic fibroblast growth factor and de novo mammalian angiogenesis.

Using the rat mesenteric-window assay, the de novo angiogenic effect of basic fibroblast growth factor (bFGF) in the intact, adult, normally vascularized test tissue was analyzed using quantitative microscopy including image analysis. Basic FGF was injected ip at doses of 10, 100, and 1000 ng twice daily for 4.5 days and the animals, which were not subjected to surgery, were sacrificed in groups every week for 6 consecutive weeks. The scale and dynamics of the angiogenic response were measured in terms of variables related to microvascular spatial expansion and density. The growth factor-induced angiogenesis in a dose-dependent, nonlinear manner and the angiogenesis displayed distinctly dose-dependent kinetics. The middle dose thus caused angiogenesis that peaked already at Day 7, thereby suggesting a direct effect. The high dose caused angiogenesis that peaked at Day 14, which also appears to be compatible with a direct effect. The low dose caused a more prolonged angiogenic response which did not peak until Day 21 or 28, depending on which variable was measured, which is indicative of an indirect effect. Clearly, the findings suggest that the molecular and cellular mechanisms of bFGF-mediated angiogenesis are dose-dependent.