Ligand-independent activation of vascular endothelial growth factor receptor 1 by low-density lipoprotein.

Abstract

Elevated serum low-density lipoprotein (LDL) is a risk factor for atherosclerotic disorders. However, prominent atherosclerosis, which has been observed in LDL receptor (LDLR)-knockout mice, has diminished the significance of LDLR as a cause of atherosclerosis, while elaborate studies have focused on the receptors for denatured LDL. Here we report that native LDL (nLDL) activates vascular endothelial growth factor (VEGF) receptor 1 (VEGFR1) but not VEGFR2 through LDLR and is as potent as VEGF in macrophage migration. Binding and co-endocytosis of VEGFR1 and LDLR were enhanced by nLDL, which is concomitant with ubiquitination-mediated degradation of VEGFR1. We propose that LDLR-mediated use of VEGFR1 by nLDL could be a potential therapeutic target in atherosclerotic disorders.

• Authors: Ryosuke Usui, Masabumi Shibuya, Shun Ishibashi, Yoshiro Maru
• Journal: EMBO reports (EMBO Rep) Vol. 8 Issue 12 Pg. 1155-61 (Dec 2007) ISSN: 1469-221X [Print] England
• PMID: 17962812 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ligands
• Lipoproteins, LDL
• Receptors, LDL
• Green Fluorescent Proteins
• Vascular Endothelial Growth Factor Receptor-1
• Vascular Endothelial Growth Factor Receptor-2

Topics

• Animals
• Blotting, Western
• CHO Cells
• Cell Line
• Cells, Cultured
• Cricetinae
• Cricetulus
• Endocytosis (drug effects)
• Green Fluorescent Proteins (genetics, metabolism)
• Humans
• Immunoprecipitation
• Ligands
• Lipoproteins, LDL (pharmacology)
• Macrophages (cytology, drug effects, metabolism)
• Mice
• Mice, Knockout
• Microscopy, Confocal
• NIH 3T3 Cells
• Phosphorylation (drug effects)
• Protein Binding (drug effects)
• Receptors, LDL (genetics, metabolism)
• Vascular Endothelial Growth Factor Receptor-1 (genetics, metabolism)
• Vascular Endothelial Growth Factor Receptor-2 (genetics, metabolism)