Vascular permeability induced by VEGF family members in vivo: Role of endogenous PAF and NO synthesis
- 17 November 2006
- journal article
- Published by Wiley in Journal of Cellular Biochemistry
- Vol. 100 (3) , 727-737
- https://doi.org/10.1002/jcb.21124
Abstract
We previously reported that vascular endothelial growth factor (VEGF) increases vascular permeability through the synthesis of endothelial platelet‐activating factor (PAF), while others reported the contribution of nitric oxide (NO). Herein, we addressed the contribution of VEGF receptors and the role played by PAF and NO in VEGF‐induced plasma protein extravasation. Using a modified Miles assay, intradermal injection in mice ears of VEGF‐A165, VEGF‐A121, and VEGF‐C (1 µM) which activate VEGFR‐2 (Flk‐1) receptor increased vascular permeability, whereas a treatment with VEGFR‐1 (Flt‐1) analogs; PlGF and VEGF‐B (1 µM) had no such effect. Pretreatment of mice with PAF receptor antagonist (LAU8080) or endothelial nitric oxide synthase (eNOS) inhibitor (L‐NAME) abrogated protein extravasation mediated by VEGF‐A165. As opposed to PAF (0.01‐1 µM), treatment with acetylcholine (ACh; up to 100 µM; inducer of NO synthesis) or sodium nitroprusside (SNP; up to 1 µM; NO donor) did not induce protein leakage. Simultaneous pretreatment of mice with eNOS and protein kinase A (PKA) inhibitors restored VEGF‐A165 vascular hyperpermeability suggesting that endogenous NO synthesis leads to PKA inhibition, which support maintenance of vascular integrity. Our data demonstrate that VEGF analogs increase vascular permeability through VEGFR‐2 activation, and that both endogenous PAF and NO synthesis contribute to VEGF‐A165‐mediated vascular permeability. However, PAF but not NO directly increases vascular permeability per se, thereby, suggesting that PAF is a direct inflammatory mediator, whereas NO serves as a cofactor in VEGF‐A165 proinflammatory activities. J. Cell. Biochem. 100: 727–737, 2007.Keywords
This publication has 35 references indexed in Scilit:
- Tyrosine Phosphorylation of VE-cadherin Prevents Binding of p120- and β-Catenin and Maintains the Cellular Mesenchymal StateJournal of Biological Chemistry, 2005
- Platelet‐activating factor increases VE‐cadherin tyrosine phosphorylation in mouse endothelial cells and its association with the PtdIns3′‐kinaseThe FASEB Journal, 2005
- Vascular endothelial growth factor stimulates differential signaling pathways in in vivo microcirculationAmerican Journal of Physiology-Heart and Circulatory Physiology, 2004
- Platelet-Activating Factor (PAF) Induces Corneal Neovascularization and Upregulates VEGF Expression in Endothelial CellsInvestigative Opthalmology & Visual Science, 2004
- Protein kinase A attenuates endothelial cell barrier dysfunction induced by microtubule disassemblyAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2004
- VEGF-mediated endothelial P-selectin translocation: role of VEGF receptors and endogenous PAF synthesisBlood, 2004
- Comparative Evaluation of FGF-2–, VEGF-A–, and VEGF-C–Induced Angiogenesis, Lymphangiogenesis, Vascular Fenestrations, and PermeabilityCirculation Research, 2004
- Relative effects of VEGF‐A and VEGF‐C on endothelial cell proliferation, migration and PAF synthesis: Role of neuropilin‐1Journal of Cellular Biochemistry, 2002
- The shortest isoform of human vascular endothelial growth factor/vascular permeability factor (VEGF/VPF121) produced by Saccharomyces cerevisiae promotes both angiogenesis and vascular permeabilityBiochimica et Biophysica Acta (BBA) - General Subjects, 1995
- Correlation between evans blue dye and radiolabeled albumin in guinea pig airways in vivoJournal of Pharmacological Methods, 1989