| 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
(Affiliation: Department of Pharmacology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.)
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| Journal | EMBO reports
(EMBO Rep)
Vol. 8
Issue 12
Pg. 1155-61
(Dec 2007)
ISSN: 1469-221X England |
| PMID | 17962812
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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| 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)
|
