エンドウ　ヤスヒロ   YASUHIRO ENDO   遠藤　康弘    所属   新潟薬科大学  医療技術学部 学部付    職種   准教授
言語種別	英語
発行・発表の年月	2014/09
形態種別	論文 - 研究論文（学術雑誌）
標題	Ezetimibe enhances macrophage reverse cholesterol transport in hamsters: contribution of hepato-biliary pathway.
執筆形態	単著（従来区分）
掲載誌名	Biochimica et biophysica acta
掲載区分	国外
巻・号・頁	1841(9),pp.1247-55
著者・共著者	Harumi Uto-Kondo,Makoto Ayaori,Grace Megumi Sotherden,Kazuhiro Nakaya,Makoto Sasaki,Makiko Yogo,Tomohiro Komatsu,Shunichi Takiguchi,Emi Yakushiji,Masatsune Ogura,Takafumi Nishida,Yasuhiro Endo,Katsunori Ikewaki
概要	Reverse cholesterol transport (RCT) is pivotal in the return of excess cholesterol from peripheral tissues to the liver for excretion in bile and eventually feces. RCT from macrophages is a critical anti-atherogenicity mechanism of HDL. As the cholesterol absorption inhibitor ezetimibe promoted RCT in mice, which lack cholesterol ester transfer protein (CETP), we investigated its effects in hamsters, which have CETP. A high-cholesterol diet (HC) increased cholesterol levels throughout lipoprotein fractions and ezetimibe markedly reduced VLDL/LDL cholesterol levels under both normal chow (NC) and HC. However, ezetimibe did not affect and reduced HDL-cholesterol levels under NC and HC, respectively. Intraperitoneal injection of (3)H-cholesterol pre-labeled macrophages in an in vivo RCT assay increased tracer accumulation in the liver but reduced it in bile under HC, and these changes were completely cancelled by ezetimibe. Under both NC and HC, ezetimibe reduced tracer levels in the liver but increased them in feces, indicating promotion of RCT in vivo. We performed a RCT assay using hamsters subjected to bile duct ligation (BDL) to clarify whether a transintestinal cholesterol efflux (TICE) pathway contributes to ezetimibe's enhancement of RCT. BDL markedly inhibited macrophage-derived (3)H-cholesterol excretion to feces and cancelled ezetimibe's stimulatory effect on RCT, suggesting that biliary cholesterol excretion is a major contributor in RCT promotion by ezetimibe but the contribution of the TICE pathway is minimal. In conclusions, ezetimibe exerts an additive anti-atherogenic property by enhancing RCT in hamsters. Our findings suggest that this property is independent of the TICE pathway.
DOI	10.1016/j.bbalip.2014.05.009
PMID	24989153