Vascular endothelial growth factor fails to acutely modulate endothelial permeability during early angiogenesis in the chick chorioallantoic membrane. 2000

L M DeFouw, and D O DeFouw
Department of Anatomy, Cell Biology, and Injury Sciences, UMDNJ-New Jersey Medical School, Newark, New Jersey 07103, USA.

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.

UI MeSH Term Description Entries
D008222 Lymphokines Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity. Lymphocyte Mediators,Mediators, Lymphocyte
D011518 Proto-Oncogene Proteins Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. Cellular Proto-Oncogene Proteins,c-onc Proteins,Proto Oncogene Proteins, Cellular,Proto-Oncogene Products, Cellular,Cellular Proto Oncogene Proteins,Cellular Proto-Oncogene Products,Proto Oncogene Products, Cellular,Proto Oncogene Proteins,Proto-Oncogene Proteins, Cellular,c onc Proteins
D002199 Capillary Permeability The property of blood capillary ENDOTHELIUM that allows for the selective exchange of substances between the blood and surrounding tissues and through membranous barriers such as the BLOOD-AIR BARRIER; BLOOD-AQUEOUS BARRIER; BLOOD-BRAIN BARRIER; BLOOD-NERVE BARRIER; BLOOD-RETINAL BARRIER; and BLOOD-TESTIS BARRIER. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (TIGHT JUNCTIONS) which may limit large molecule movement. Microvascular Permeability,Permeability, Capillary,Permeability, Microvascular,Vascular Permeability,Capillary Permeabilities,Microvascular Permeabilities,Permeabilities, Capillary,Permeabilities, Microvascular,Permeabilities, Vascular,Permeability, Vascular,Vascular Permeabilities
D002642 Chick Embryo The developmental entity of a fertilized chicken egg (ZYGOTE). The developmental process begins about 24 h before the egg is laid at the BLASTODISC, a small whitish spot on the surface of the EGG YOLK. After 21 days of incubation, the embryo is fully developed before hatching. Embryo, Chick,Chick Embryos,Embryos, Chick
D002823 Chorion The outermost extra-embryonic membrane surrounding the developing embryo. In REPTILES and BIRDS, it adheres to the shell and allows exchange of gases between the egg and its environment. In MAMMALS, the chorion evolves into the fetal contribution of the PLACENTA. Chorions
D004730 Endothelium, Vascular Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components. Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D000482 Allantois An extra-embryonic membranous sac derived from the YOLK SAC of REPTILES; BIRDS; and MAMMALS. It lies between two other extra-embryonic membranes, the AMNION and the CHORION. The allantois serves to store urinary wastes and mediate exchange of gas and nutrients for the developing embryo. Allantoic Membrane,Membrane, Allantoic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D016228 Endothelial Growth Factors These growth factors are soluble mitogens secreted by a variety of organs. The factors are a mixture of two single chain polypeptides which have affinity to heparin. Their molecular weight are organ and species dependent. They have mitogenic and chemotactic effects and can stimulate endothelial cells to grow and synthesize DNA. The factors are related to both the basic and acidic FIBROBLAST GROWTH FACTORS but have different amino acid sequences. Endothelial Cell-Derived Growth Factors,alpha-Endothelial Growth Factor,beta-Endothelial Growth Factor,ECDGF,Endo-GF,Endothelial Growth Factor,Endothelial Growth Factor Polypeptides,Endothelial Cell Derived Growth Factors,Growth Factor, Endothelial,Growth Factor, alpha-Endothelial,Growth Factor, beta-Endothelial,Growth Factors, Endothelial,alpha Endothelial Growth Factor,beta Endothelial Growth Factor

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