TY - JOUR
T1 - Nerve Growth Factor (NGF) promotes angiogenesis in the quail chorioallantoic membrane
AU - Lazarovici, Philip
AU - Gazit, Aviv
AU - Staniszewska, Izabela
AU - Marcinkiewicz, Cezary
AU - Lelkes, Peter I.
PY - 2006/1
Y1 - 2006/1
N2 - 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 μ g. 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 embrayos. This effect was similar to that of 0.5 μg rhVEGF (1.290 ± 0.021, p < .001) and 1.5 μ rhFGF (1.264 ± 0.028, p < .001). The mouse NGF-induced angiogenic effect was blocked by 1 μM K252a (1.149 ± 0.118, p < .001), an antagonist of the NGF/trkA receptor, but not by 1 μM 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.
AB - 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 μ g. 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 embrayos. This effect was similar to that of 0.5 μg rhVEGF (1.290 ± 0.021, p < .001) and 1.5 μ rhFGF (1.264 ± 0.028, p < .001). The mouse NGF-induced angiogenic effect was blocked by 1 μM K252a (1.149 ± 0.118, p < .001), an antagonist of the NGF/trkA receptor, but not by 1 μM 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.
KW - bFGF
KW - CAM assay
KW - K252a
KW - NGF
KW - SU-5416
KW - VEGF
UR - http://www.scopus.com/inward/record.url?scp=33646505056&partnerID=8YFLogxK
U2 - 10.1080/10623320600669053
DO - 10.1080/10623320600669053
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C2 - 16885067
AN - SCOPUS:33646505056
SN - 1062-3329
VL - 13
SP - 51
EP - 59
JO - Endothelium: Journal of Endothelial Cell Research
JF - Endothelium: Journal of Endothelial Cell Research
IS - 1
ER -