FGF-2 dependent angiogenesis is a latent phenotype in basic fibroblast growth factor transgenic mice

Overexpression of basic fibroblast growth factor (FGF-2) in transgenic (TgFGF2) mice results in a chondrodysplasia as the principle phenotype. Here we report a second phenotype in TgFGF2 mice that was previously undetected: A predisposition to angiogenic reactions with subsequent amplified angiogenesis that are both FGF-2 dependent. We used subcutaneous injection of extracellular matrix as an angiogenic assay. The matrix formed vascularized cysts in the TgFGF2 group after seven days, whereas the non-transgenic (NTg) group developed avascular cysts. Cysts from the TgFGF2 group contained 3-7X more hemoglobin (Hb), two-fold more vonWillebrand Factor (VWF), and 150X more FGF-2 than cysts from the NTg control group. Significant angiogenic reactions occurred only in the TgFGF2 group that express FGF-2 from the transgene. The TgFGF2 mice, therefore, constitute a unique experimental system to study FGF-2 dependent angiogenesis because they have no spontaneous or inherent vascular defects, but provision of an angiogenic substrate results in an amplified angiogenic response. In addition, we report development of an ELISA for VWF that provides a sensitive, quantitative assay for angiogenesis.