Liver X receptor modulators: Effects on lipid metabolism and potential use in the treatment of atherosclerosis

被引：79

作者：

Fievet, C. ^{[1
,2
,3
]}

Staels, B. ^{[1
,2
,3
]}

机构：

[1] Inst Pasteur, INSERM, U545, F-59019 Lille, France

[2] Univ Lille 2, Fac Sci Pharmaceut & Biol, F-59006 Lille, France

[3] Fac Med, F-59006 Lille, France

来源：

BIOCHEMICAL PHARMACOLOGY | 2009年 / 77卷 / 08期

关键词：

LXRs; Cholesterol homeostasis; Liver steatosis; LXR ligands; Atherosclerosis; PHOSPHOLIPID TRANSFER PROTEIN; DENSITY-LIPOPROTEIN RECEPTOR; CELLULAR CHOLESTEROL EFFLUX; ELEMENT-BINDING PROTEIN; LXR-ALPHA; NUCLEAR RECEPTOR; OXYSTEROL RECEPTOR; HDL CHOLESTEROL; GENE-EXPRESSION; PHARMACOLOGICAL ACTIVATION;

D O I：

10.1016/j.bcp.2008.11.026

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Liver X receptors (LXRs) are nuclear receptors that play a crucial role in regulating the expression of genes involved in lipid metabolism. Ligand activation of LXRs improves cholesterol homeostasis via multiple coordinated effects, and this function is likely to explain in part the protective effects of LXR activation on atherosclerosis reported in animal models. However, LXR activation may also induce undesirable side effects, such as lipogenesis and hypertriglyceridemia. This review discusses the potential to develop LXR modulators as therapeutic agents for atherosclerosis. (C) 2008 Elsevier Inc. All rights reserved.

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收藏

页码：1316 / 1327

页数：12

相关论文

共 99 条

[1] A novel principle for partial agonism of liver X receptor ligands - Competitive recruitment of activators and repressors [J].

Albers, M ;

Blume, B ;

Schlueter, T ;

Wright, MB ;

Kober, I ;

Kremoser, C ;

Deuschle, U ;

Koegl, M .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (08) :4920-4930

[2] Hepatic cholesterol metabolism and resistance to dietary cholesterol in LXRβ-deficient mice [J].

Alberti, S ;

Schuster, G ;

Parini, P ;

Feltkamp, D ;

Diczfalusy, U ;

Rudling, M ;

Angelin, B ;

Björkhem, I ;

Pettersson, S ;

Gustafsson, JÅ .

JOURNAL OF CLINICAL INVESTIGATION, 2001, 107 (05) :565-573

[3] Niemann-Pick C1 like 1 protein is critical for intestinal cholesterol absorption [J].

Altmann, SW ;

Davis, HR ;

Zhu, LJ ;

Yao, XR ;

Hoos, LM ;

Tetzloff, G ;

Iyer, SPN ;

Maguire, M ;

Golovko, A ;

Zeng, M ;

Wang, LQ ;

Murgolo, N ;

Graziano, MP .

SCIENCE, 2004, 303 (5661) :1201-1204

[4] A role for the apoptosis inhibitory factor AIM/Spα/Api6 in atherosclerosis development [J].

Arai, S ;

Shelton, JM ;

Chen, MY ;

Bradley, MN ;

Castrillo, A ;

Bookout, AL ;

Mak, PA ;

Edwards, PA ;

Mangelsdorf, DJ ;

Tontonoz, P ;

Miyazaki, T .

CELL METABOLISM, 2005, 1 (03) :201-213

[5] Ligand activation of LXRβ reverses atherosclerosis and cellular cholesterol overload in mice lacking LXRα and apoE [J].

Bradley, Michelle N. ;

Hong, Cynthia ;

Chen, Mingyi ;

Joseph, Sean B. ;

Wilpitz, Damien C. ;

Wang, Xuping ;

Lusis, Aldons J. ;

Collins, Allan ;

Hseuh, Willa A. ;

Collins, Jon L. ;

Tangirala, Rajendra K. ;

Tontonoz, Peter .

JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (08) :2337-2346

[6] A RECEPTOR-MEDIATED PATHWAY FOR CHOLESTEROL HOMEOSTASIS [J].

BROWN, MS ;

GOLDSTEIN, JL .

SCIENCE, 1986, 232 (4746) :34-47

[7] Tissue-specific induction of intestinal ABCA1 expression with a liver x receptor agonist raises plasma HDL cholesterol levels [J].

Brunham, Liam R. ;

Kruit, Janine K. ;

Pape, Terry D. ;

Parks, John S. ;

Kuipers, Folkert ;

Hayden, Michael R. .

CIRCULATION RESEARCH, 2006, 99 (07) :672-674

[8] Intestinal ABCA1 directly contributes to HDL biogenesis in vivo [J].

Brunham, LR ;

Kruit, JK ;

Iqbal, J ;

Fievet, C ;

Timmins, JM ;

Pape, TD ;

Coburn, BA ;

Bissada, N ;

Staels, B ;

Groen, AK ;

Hussain, MM ;

Parks, JS ;

Kuipers, F ;

Hayden, MR .

JOURNAL OF CLINICAL INVESTIGATION, 2006, 116 (04) :1052-1062

[9] Phospholipid transfer protein is regulated by liver X receptors in vivo [J].

Cao, GQ ;

Beyer, TP ;

Yang, XP ;

Schmidt, RJ ;

Zhang, YY ;

Bensch, WR ;

Kauffman, RF ;

Gao, H ;

Ryan, TP ;

Liang, Y ;

Eacho, PI ;

Jiang, XC .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (42) :39561-39565

[10] Liver X receptor-dependent repression of matrix metalloproteinase-9 expression in macrophages [J].

Castrillo, A ;

Joseph, SB ;

Marathe, C ;

Mangelsdorf, DJ ;

Tontonoz, P .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (12) :10443-10449

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