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EMBO reports 8, 12, 1155–1161 (2007)
doi:10.1038/sj.embor.7401103
AOP Published online: 26 October 2007
Ligand-independent activation of vascular endothelial growth factor receptor 1 by low-density lipoprotein
Ryosuke Usui1, Masabumi Shibuya2, Shun Ishibashi3 & Yoshiro Maru1, 4
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1 Department of Pharmacology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan
2 Department of Genetics, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
3 Division of Endocrinology and Metabolism, Department of Internal Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan
4 IREIIMS, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan
To whom correspondence should be addressed
Yoshiro Maru Tel: +81 3 5269 7417; Fax: +81 3 5269 7417; E-mail: ymaru@research.twmu.ac.jp
Received 20 February 2007; Accepted 11 September 2007; Published online 26 October 2007.
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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.
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