Ligand-independent activation of vascular endothelial growth factor receptor 1 by low-density lipoprotein.
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.
Mesh Terms:
Animals, Blotting, Western, CHO Cells, Cell Line, Cells, Cultured, Cricetinae, Cricetulus, Endocytosis, Green Fluorescent Proteins, Humans, Immunoprecipitation, Ligands, Lipoproteins, LDL, Macrophages, Mice, Mice, Knockout, Microscopy, Confocal, NIH 3T3 Cells, Phosphorylation, Protein Binding, Receptors, LDL, Vascular Endothelial Growth Factor Receptor-1, Vascular Endothelial Growth Factor Receptor-2
Animals, Blotting, Western, CHO Cells, Cell Line, Cells, Cultured, Cricetinae, Cricetulus, Endocytosis, Green Fluorescent Proteins, Humans, Immunoprecipitation, Ligands, Lipoproteins, LDL, Macrophages, Mice, Mice, Knockout, Microscopy, Confocal, NIH 3T3 Cells, Phosphorylation, Protein Binding, Receptors, LDL, Vascular Endothelial Growth Factor Receptor-1, Vascular Endothelial Growth Factor Receptor-2
EMBO Rep.
Date: Dec. 01, 2007
PubMed ID: 17962812
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