Ken Sugimoto
Department Kawasaki Medical School Kawasaki Medical School, Department of General Geriatric Medicine, Position Professor |
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Article types | 原著 |
Language | English |
Peer review | Peer reviewed |
Title | Oxidized LDL (oxLDL) activates the angiotensin II type 1 receptor by binding to the lectin-like oxLDL receptor. |
Journal | Formal name:FASEB journal : official publication of the Federation of American Societies for Experimental Biology Abbreviation:FASEB J ISSN code:15306860/08926638 |
Domestic / Foregin | Foregin |
Volume, Issue, Page | 29(8),pp.3342-3356 |
Author and coauthor | Yamamoto Koichi, Kakino Akemi, Takeshita Hikari, Hayashi Norihiro, Li Lei, Nakano Atsushi, Hanasaki-Yamamoto Hiroko, Fujita Yoshiko, Imaizumi Yuki, Toyama-Yokoyama Serina, Nakama Chikako, Kawai Tatsuo, Takeda Masao, Hongyo Kazuhiro, Oguro Ryosuke, Maekawa Yoshihiro, Itoh Norihisa, Takami Yoichi, Onishi Miyuki, Takeya Yasushi, Sugimoto Ken, Kamide Kei, Nakagami Hironori, Ohishi Mitsuru, Kurtz Theodore W, Sawamura Tatsuya, Rakugi Hiromi |
Publication date | 2015/08 |
Summary | The angiotensin II type 1 receptor (AT1) is a 7-transmembrane domain GPCR that when activated by its ligand angiotensin II, generates signaling events promoting vascular dysfunction and the development of cardiovascular disease. Here, we show that the single-transmembrane oxidized LDL (oxLDL) receptor (LOX-1) resides in proximity to AT1 on cell-surface membranes and that binding of oxLDL to LOX-1 can allosterically activate AT1-dependent signaling events. oxLDL-induced signaling events in human vascular endothelial cells were abolished by knockdown of AT1 and inhibited by AT1 blockade (ARB). oxLDL increased cytosolic G protein by 350% in Chinese hamster ovary (CHO) cells with genetically induced expression of AT1 and LOX-1, whereas little increase was observed in CHO cells expressing only LOX-1. Immunoprecipitation and in situ proximity ligation assay (PLA) assays in CHO cells revealed the presence of cell-surface complexes involving LOX-1 and AT1. Chimeric analysis showed that oxLDL-induced AT1 signaling events are mediated via interactions between the intracellular domain of LOX-1 and AT1 that activate AT1. oxLDL-induced impairment of endothelium-dependent vascular relaxation of vascular ring from mouse thoracic aorta was abolished by ARB or genetic deletion of AT1. These findings reveal a novel pathway for AT1 activation and suggest a new mechanism whereby oxLDL may be promoting risk for cardiovascular disease. |
DOI | 10.1096/fj.15-271627 |
PMID | 25877213 |