Vegf-e Activates Endothelial Nitric Oxide Synthase to Induce Angiogenesis Via Cgmp and Pkg-independent Pathways.
From: Department of Reproductive and Vascular Biology, Centre for Cardiovascular Sciences, Institute of Biomedical Research, The Medical School, University of Birmingham, Edgbaston, UK.
Biochemical and biophysical research communications
- Publish Date: Jul 2006
- ISSN: 0006-291X
- Volume: 345
- Issue: 4
- Pages: 1275-82
- Medium: Print
- Language: English
- Citation (JAMA): Cudmore Melissa, Ahmad Shakil, Al-Ani Bahjat, et al. Vegf-e Activates Endothelial Nitric Oxide Synthase to Induce Angiogenesis Via Cgmp and Pkg-independent Pathways.. Biochem. Biophys. Res. Commun. Jul 2006;345:1275-82
Abstract
Vascular endothelial growth factor-A (VEGF), which binds to both VEGF receptor-1 (Flt1) and VEGFR-2 (KDR/Flk-1), requires nitric oxide (NO) to induce angiogenesis in a cGMP-dependent manner. Here we show that VEGF-E, a VEGFR-2-selective ligand stimulates NO release and tube formation in human umbilical vein endothelial cells (HUVEC). Inhibition of phospholipase Cgamma (PLCgamma) with U73122 abrogated VEGF-E induced endothelial cell migration, tube formation and NO release. Inhibition of endothelial nitric oxide synthase (eNOS) using l-NNA blocked VEGF-E-induced NO release and angiogenesis. Pre-incubation of HUVEC with the soluble guanylate cyclase inhibitor, ODQ, or the protein kinase G (PKG) inhibitor, KT-5823, had no effect on angiogenesis suggesting that the action of VEGF-E is cGMP-independent. Our data provide the first demonstration that VEGFR-2-mediated NO signaling and subsequent angiogenesis is through a mechanism that is dependent on PLCgamma but independent of cGMP and PKG.
Mesh Headings (Keywords): Animals, Carbazoles, Cell Movement, Cells, Cultured, Cyclic GMP, Cyclic GMP-Dependent Protein Kinases, Dose-Response Relationship, Drug, Endothelial Cells, Enzyme Activation, Enzyme Inhibitors, Estrenes, Humans, Indoles, Neovascularization, Physiologic, Nitric Oxide, Nitric Oxide Synthase, Nitroarginine, Phospholipase C gamma, Phosphorylation, Pyrrolidinones, Signal Transduction, Swine, Vascular Endothelial Growth Factor Receptor-2, Viral Proteins
Check for Full Text / PubMed Unique Identifier (PMID): 16725109
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