BASIC FIBROBLAST GROWTH-FACTOR AND DE-NOVO MAMMALIAN ANGIOGENESIS

Using the rat mesenteric-window assay, the de novo angiogenic effect o f basic fibroblast growth factor (bFGF) in the intact, adult, normally vascularized test tissue was analyzed using quantitative microscopy i ncluding 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 cons ecutive weeks. The scale and dynamics of the angiogenic response were measured in terms of variables related to microvascular spatial expans ion and density. The growth factor-induced angiogenesis in a dose-depe ndent, nonlinear manner and the angiogenesis displayed distinctly dose -dependent kinetics. The middle dose thus caused angiogenesis that pea ked already at Day 7, thereby suggesting a direct effect. The high dos e 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 o n which variable was measured, which is indicative of an indirect effe ct. Clearly, the findings suggest that the molecular and cellular mech anisms of bFGF-mediated angiogenesis are dose-dependent. (C) 1994 Acad emic Press, Inc.