Vascular endothelial growth factor fails to acutely modulate endothelial permeability during early angiogenesis in the chick chorioallantoic membrane.
The angiogenic endothelium of the chorioallantoic membrane (CAM) offers minimal restriction to macromolecular efflux at Day 4.5 of the normal 21-day chick gestation. Vascular endothelial growth factor (VEGF)-specific Flk-1 and Flt-1 tyrosine phosphorylation was observed at Day 4.5 by receptor immunoprecipitation and requisite immunoblotting. Further, general inhibition of tyrosine phosphorylation by either genistein or tyrphostin (10(-4) M) served to reduce FITC-Dextran 40 extravasation at Day 4.5. Likewise, anti-VEGF, but not anti-FGF-2 mAb, abolished the temporal endothelial hyperpermeability. These results are consistent with the established permeability-enhancing function of VEGF. Normal differentiation of the restrictive CAM endothelial barrier at Day 5. 0 was associated with reduced Flk-1 and Flt-1 expression, but sustained tyrosine phosphorylation of the residual RTKs. Moreover, inhibition of VEGF/RTK activity by anti-VEGF mAb at Day 5.0 did not enhance normal endothelial barrier function. Likewise, neither VEGF (5 x 10(-4) to 10(-15) M) nor PlGF (10(-6) to 10(-8) M), which selectively binds Flt-1, served to increase FITC-Dextran 40 efflux at Day 5.0. Together, these results are consistent with the suggestion that down-regulation of the permeability-related VEGF signal correlates temporally with the ontogeny of restrictive endothelial barrier function during angiogenesis in vivo.
DeFouw
L M
LM
Department of Anatomy, Cell Biology, and Injury Sciences, UMDNJ-New Jersey Medical School, Newark, New Jersey 07103, USA.
DeFouw
D O
DO
D000482:Allantois / Q000098:blood supply* / Q000187:drug effects*; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply* / Q000187:drug effects*; D016228:Endothelial Growth Factors / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects; D008222:Lymphokines / Q000494:pharmacology*; D018919:Neovascularization, Physiologic; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1