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T‐0901317, a synthetic liver X receptor ligand, inhibits development of atherosclerosis in LDL receptor‐deficient mice
Author(s) -
Terasaka Naoki,
Hiroshima Ayano,
Koieyama Tadashi,
Ubukata Naoko,
Morikawa Yuka,
Nakai Daisuke,
Inaba Toshimori
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)03578-0
Subject(s) - liver x receptor , ldl receptor , cholesterol , endocrinology , medicine , reverse cholesterol transport , receptor , nuclear receptor , lipogenesis , liver x receptor alpha , lipoprotein , chemistry , lipid metabolism , biology , biochemistry , transcription factor , gene
Liver X receptors (LXRα and LXRβ) are nuclear receptors, which are important regulators of cholesterol and lipid metabolism. LXRs control genes involved in cholesterol efflux in macrophages, bile acid synthesis in liver and intestinal cholesterol absorption. LXRs also regulate genes participating in lipogenesis. To determine whether the activation of LXR promotes or inhibits development of atherosclerosis, T‐0901317, a synthetic LXR ligand, was administered to low density lipoprotein receptor (LDLR) −/− mice. T‐0901317 significantly reduced the atherosclerotic lesions in LDLR −/− mice without affecting plasma total cholesterol levels. This anti‐atherogenic effect correlated with the plasma concentration of T‐0901317, but not with high density lipoprotein cholesterol, which was increased by T‐0901317. In addition, we observed that T‐0901317 increased expression of ATP binding cassette A1 in the lesions in LDLR −/− mice as well as in mouse peritoneal macrophages. T‐0901317 also significantly induced cholesterol efflux activity in peritoneal macrophages. These results suggest that LXR ligands may be useful therapeutic agents for the treatment of atherosclerosis.