Nerve growth factor (NGF) promotes angiogenesis in the quail chorioallantoic membrane.
Angiogenesis, the formation of new blood vessels, is tightly regulated by growth factors, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). The authors hypothesize that nerve growth factor (NGF), a well known neurotrophin, may play a direct angiogenic role. To test this hypothesis, the authors measured the effects of NGF on the natural vascularization of the quail chorioallantoic membrane (CAM). The angiogenic effect of NGF was compared to that of human recombinant VEGF165 (rhVEGF) and basic FGF (rhbFGF). In comparison to phosphate-buffered saline-treated controls, NGFs from different biological sources (mouse, viper, and cobra) increased the rate of angiogenesis in a dose-dependent fashion from 0.5 to 5 microg. For quantitative morphometry, grayscale images of the blood vessels end points of the CAM arteries were binarized for visualization and skeletonized for quantization by fractal analysis. In mouse NGF-treated embryos the fractal dimension (Df), indicative of arterial vessel length and density, increased to 1.266 +/- 0.021 compared to 1.131 +/- 0.018 (p < .001) for control embryos. This effect was similar to that of 0.5 microg rhVEGF (1.290 +/- 0.021, p < .001) and 1.5 microg rhbFGF (1.264 +/- 0.028, p < .001). The mouse NGF-induced angiogenic effect was blocked by 1 microM K252a (1.149 +/- 0.018, p < .001), an antagonist of the NGF/trkA receptor, but not by 1 microM SU-5416 (1.263 +/- 0.029, p < .001), the VEGF/Flk1 receptor antagonist, indicating a direct, selective angiogenic effect of NGF via quail embryo trkA receptor activation. These results confirm previous observations that NGF has angiogenic activity and suggest that this neurotrophin may also play an important role in the cardiovascular system, besides its well-known effects in the nervous system. The angiogenic properties of NGF may be beneficial in engineering new blood vessels and for developing novel antiangiogenesis therapies for cancer.
Lazarovici
Philip
P
School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania, USA.
Gazit
Aviv
A
Staniszewska
Izabela
I
Marcinkiewicz
Cezary
C
Lelkes
Peter I
PI
D043925:Angiogenesis Inducing Agents / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development; D049109:Cell Proliferation / Q000187:drug effects; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects* / Q000196:embryology; D003370:Coturnix; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000098:blood supply; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D017709:Fractals; D006801:Humans; D019044:Image Cytometry / Q000379:methods; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D020932:Nerve Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D009924:Organ Culture Techniques; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D013045:Species Specificity; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D043925:Angiogenesis Inducing Agents; D011993:Recombinant Fusion Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D020932:Nerve Growth Factor