スギモト　ケン   Ken Sugimoto   杉本　研    所属   川崎医科大学  医学部 臨床医学　総合老年医学    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Oxidized LDL (oxLDL) activates the angiotensin II type 1 receptor by binding to the lectin-like oxLDL receptor.
掲載誌名	正式名：FASEB journal : official publication of the Federation of American Societies for Experimental Biology 略　 称：FASEB J ISSNコード：15306860/08926638
掲載区分	国外
巻・号・頁	29(8),pp.3342-3356
著者・共著者	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
発行年月	2015/08
概要	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