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

Biochemical Pharmacology

Volumn 77, Issue 8, 2009, Pages 1316-1327

  Fievet C ^a,b,c   Staels, B ^a,b,c  

^a INSTITUT PASTEUR DE LILLE   (France)

^b INSERM   (France)

^c UNIV LILLE   (France)

Author keywords

Atherosclerosis; Cholesterol homeostasis; Liver steatosis; LXR ligands; LXRs

Indexed keywords

LIVER X RECEPTOR;

ARTICLE; ATHEROSCLEROSIS; CHOLESTEROL TRANSPORT; FATTY ACID METABOLISM; GENE EXPRESSION REGULATION; HYPERTRIGLYCERIDEMIA; LIPID METABOLISM; LIPOGENESIS; PRIORITY JOURNAL;

EID: 62549085567     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bcp.2008.11.026     Document Type: Note

References (99)

1. Willy P.J., Umesono K., Ong E.S., Evans R.M., Heyman R.A., and Mangelsdorf D.J. LXR, a nuclear receptor that defines a distinct retinoid response pathway. Genes Dev 9 9 (1995) 1033-1045
2. Repa J.J., Turley S.D., Lobaccaro J.A., Medina J., Li L., Lustig K., et al. Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers. Science 289 5484 (2000) 1524-1529
3. Wagner B.L., Valledor A.F., Shao G., Daige C.L., Bischoff E.D., Petrowski M., et al. Promoter-specific roles for liver X receptor/corepressor complexes in the regulation of ABCA1 and SREBP1 gene expression. Mol Cell Biol 23 16 (2003) 5780-5789
4. Glass C.K., and Rosenfeld M.G. The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev 14 2 (2000) 121-141
5. Repa J.J., and Mangelsdorf D.J. The role of orphan nuclear receptors in the regulation of cholesterol homeostasis. Annu Rev Cell Dev Biol 16 459-81 (2000) 459-481
6. Prufer K., and Boudreaux J. Nuclear localization of liver X receptor alpha and beta is differentially regulated. J Cell Biochem 100 1 (2007) 69-85
7. Lehmann J.M., Kliewer S.A., Moore L.B., Smith-Oliver T.A., Oliver B.B., Su J.L., et al. Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway. J Biol Chem 272 6 (1997) 3137-3140
8. Yang C., McDonald J.G., Patel A., Zhang Y., Umetani M., Xu F., et al. Sterol intermediates from cholesterol biosynthetic pathway as liver X receptor ligands. J Biol Chem 281 38 (2006) 27816-27826
9. Heverin M., Meaney S., Brafman A., Shafir M., Olin M., Shafaati M., et al. Studies on the cholesterol-free mouse: strong activation of LXR-regulated hepatic genes when replacing cholesterol with desmosterol. Arterioscler Thromb Vasc Biol 27 10 (2007) 2191-2197
10. Nomiyama T., and Bruemmer D. Liver X receptors as therapeutic targets in metabolism and atherosclerosis. Curr Atheroscler Rep 10 1 (2008) 88-95
11. Joseph S.B., McKilligin E., Pei L., Watson M.A., Collins A.R., Laffitte B.A., et al. Synthetic LXR ligand inhibits the development of atherosclerosis in mice. Proc Natl Acad Sci USA 99 11 (2002) 7604-7609
12. Hu B., Collini M., Unwalla R., Miller C., Singhaus R., Quinet E., et al. Discovery of phenyl acetic acid substituted quinolines as novel liver X receptor agonists for the treatment of atherosclerosis. J Med Chem 49 21 (2006) 6151-6154
13. Peng D., Hiipakka R.A., Dai Q., Guo J., Reardon C.A., Getz G.S., et al. Antiatherosclerotic effects of a novel synthetic tissue-selective steroidal liver X receptor agonist in low-density lipoprotein receptor-deficient mice. J Pharmacol Exp Ther 327 2 (2008) 332-342
14. Kratzer A., Buchebner M., Pfeifer T., Becker T.M., Uray G., Miyazaki M., et al. Synthetic LXR agonist attenuates plaque formation in apoE-deficient mice without inducing liver steatosis and hypertriglyceridemia. J Lipid Res (2008)
15. Terasaka N., Hiroshima A., Koieyama T., Ubukata N., Morikawa Y., Nakai D., et al. T-0901317, a synthetic liver X receptor ligand, inhibits development of atherosclerosis in LDL receptor-deficient mice. FEBS Lett 536 1-3 (2003) 6-11
16. Brunham L.R., Kruit J.K., Iqbal J., Fievet C., Timmins J.M., Pape T.D., et al. Intestinal ABCA1 directly contributes to HDL biogenesis in vivo. J Clin Invest 116 4 (2006) 1052-1062
17. Repa J.J., Berge K.E., Pomajzl C., Richardson J.A., Hobbs H., and Mangelsdorf D.J. Regulation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 by the liver X receptors alpha and beta. J Biol Chem 277 21 (2002) 18793-18800
18. Altmann S.W., Davis Jr. H.R., Zhu L.J., Yao X., Hoos L.M., Tetzloff G., et al. Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science 303 5661 (2004) 1201-1204
19. Duval C., Touche V., Tailleux A., Fruchart J.C., Fievet C., Clavey V., et al. Niemann-Pick C1 like 1 gene expression is down-regulated by LXR activators in the intestine. Biochem Biophys Res Commun 340 4 (2006) 1259-1263
20. Brown M.S., and Goldstein J.L. A receptor-mediated pathway for cholesterol homeostasis. Science 232 4746 (1986) 34-47
21. Peet D.J., Turley S.D., Ma W., Janowski B.A., Lobaccaro J.M., Hammer R.E., et al. Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXR alpha. Cell 93 5 (1998) 693-704
22. Alberti S., Schuster G., Parini P., Feltkamp D., Diczfalusy U., Rudling M., et al. Hepatic cholesterol metabolism and resistance to dietary cholesterol in LXRbeta-deficient mice. J Clin Invest 107 5 (2001) 565-573
23. Wang Y., Rogers P.M., Su C., Varga G., Stayrook K.R., and Burris T.P. Regulation of cholesterologenesis by the oxysterol receptor, LXR{alpha}. J Biol Chem 283 39 (2008) 26332-26339
24. Ishimoto K., Tachibana K., Sumitomo M., Omote S., Hanano I., Yamasaki D., et al. Identification of human low-density lipoprotein receptor as a novel target gene regulated by liver X receptor alpha. FEBS Lett 580 20 (2006) 4929-4933
25. Francis G.A., Knopp R.H., and Oram J.F. Defective removal of cellular cholesterol and phospholipids by apolipoprotein A-I in Tangier disease. J Clin Invest 96 1 (1995) 78-87
26. Wang N., Ranalletta M., Matsuura F., Peng F., and Tall A.R. LXR-induced redistribution of ABCG1 to plasma membrane in macrophages enhances cholesterol mass efflux to HDL. Arterioscler Thromb Vasc Biol 26 6 (2006) 1310-1316
27. Rigamonti E., Helin L., Lestavel S., Mutka A.L., Lepore M., Fontaine C., et al. Liver X receptor activation controls intracellular cholesterol trafficking and esterification in human macrophages. Circ Res 97 7 (2005) 682-689
28. Laffitte B.A., Repa J.J., Joseph S.B., Wilpitz D.C., Kast H.R., Mangelsdorf D.J., et al. LXRs control lipid-inducible expression of the apolipoprotein E gene in macrophages and adipocytes. Proc Natl Acad Sci USA 98 2 (2001) 507-512
29. Mak P.A., Laffitte B.A., Desrumaux C., Joseph S.B., Curtiss L.K., Mangelsdorf D.J., et al. Regulated expression of the apolipoprotein E/C-I/C-IV/C-II gene cluster in murine and human macrophages. A critical role for nuclear liver X receptors alpha and beta. J Biol Chem 277 35 (2002) 31900-31908
30. Liang Y., Jiang X.C., Liu R., Liang G., Beyer T.P., Gao H., et al. Liver X receptors (LXRs) regulate apolipoprotein AIV-implications of the antiatherosclerotic effect of LXR agonists. Mol Endocrinol 18 8 (2004) 2000-2010
31. Laffitte B.A., Joseph S.B., Chen M., Castrillo A., Repa J., Wilpitz D., et al. The phospholipid transfer protein gene is a liver X receptor target expressed by macrophages in atherosclerotic lesions. Mol Cell Biol 23 6 (2003) 2182-2191
32. Cao G., Beyer T.P., Yang X.P., Schmidt R.J., Zhang Y., Bensch W.R., et al. Phospholipid transfer protein is regulated by liver X receptors in vivo. J Biol Chem 277 42 (2002) 39561-39565
33. Luo Y., and Tall A.R. Sterol upregulation of human CETP expression in vitro and in transgenic mice by an LXR element. J Clin Invest 105 4 (2000) 513-520
34. Masson D., Staels B., Gautier T., Desrumaux C., Athias A., Le Guern N., et al. Cholesteryl ester transfer protein modulates the effect of liver X receptor agonists on cholesterol transport and excretion in the mouse. J Lipid Res 45 3 (2004) 543-550
35. Zhang Y., Repa J.J., Gauthier K., and Mangelsdorf D.J. Regulation of lipoprotein lipase by the oxysterol receptors, LXRalpha and LXRbeta. J Biol Chem 276 46 (2001) 43018-43024
36. Wang N., Lan D., Chen W., Matsuura F., and Tall A.R. ATP-binding cassette transporters G1 and G4 mediate cellular cholesterol efflux to high-density lipoproteins. Proc Natl Acad Sci USA 101 26 (2004) 9774-9779
37. Costet P., Luo Y., Wang N., and Tall A.R. Sterol-dependent transactivation of the ABC1 promoter by the liver X receptor/retinoid X receptor. J Biol Chem 275 36 (2000) 28240-28245
38. Engel T., Lorkowski S., Lueken A., Rust S., Schluter B., Berger G., et al. The human ABCG4 gene is regulated by oxysterols and retinoids in monocyte-derived macrophages. Biochem Biophys Res Commun 288 2 (2001) 483-488
39. Venkateswaran A., Laffitte B.A., Joseph S.B., Mak P.A., Wilpitz D.C., Edwards P.A., et al. Control of cellular cholesterol efflux by the nuclear oxysterol receptor LXR alpha. Proc Natl Acad Sci USA 97 22 (2000) 12097-12102
40. Claudel T., Leibowitz M.D., Fievet C., Tailleux A., Wagner B., Repa J.J., et al. Reduction of atherosclerosis in apolipoprotein E knockout mice by activation of the retinoid X receptor. Proc Natl Acad Sci USA 98 5 (2001) 2610-2615
41. Schuster G.U., Parini P., Wang L., Alberti S., Steffensen K.R., Hansson G.K., et al. Accumulation of foam cells in liver X receptor-deficient mice. Circulation 106 9 (2002) 1147-1153
42. Naik S.U., Wang X., Da Silva J.S., Jaye M., Macphee C.H., Reilly M.P., et al. Pharmacological activation of liver X receptors promotes reverse cholesterol transport in vivo. Circulation 113 1 (2006) 90-97
43. Rader D.J. Liver X receptor and farnesoid X receptor as therapeutic targets. Am J Cardiol 100 11A (2007) n15-n19
44. Yu L., York J., von Bergmann K., Lutjohann D., Cohen J.C., and Hobbs H.H. Stimulation of cholesterol excretion by the liver X receptor agonist requires ATP-binding cassette transporters G5 and G8. J Biol Chem 278 18 (2003) 15565-15570
45. Plosch T., Bloks V.W., Terasawa Y., Berdy S., Siegler K., Van Der S.F., et al. Sitosterolemia in ABC-transporter G5-deficient mice is aggravated on activation of the liver-X receptor. Gastroenterology 126 1 (2004) 290-300
46. Uppal H., Saini S.P., Moschetta A., Mu Y., Zhou J., Gong H., et al. Activation of LXRs prevents bile acid toxicity and cholestasis in female mice. Hepatology 45 2 (2007) 422-432
47. Uppal H., Zhai Y., Gangopadhyay A., Khadem S., Ren S., Moser J.A., et al. Activation of liver X receptor sensitizes mice to gallbladder cholesterol crystallization. Hepatology 47 4 (2008) 1331-1342
48. Chiang J.Y., Kimmel R., and Stroup D. Regulation of cholesterol 7alpha-hydroxylase gene (CYP7A1) transcription by the liver orphan receptor (LXRalpha). Gene 262 1/2 (2001) 257-265
49. Kotokorpi P., Ellis E., Parini P., Nilsson L.M., Strom S., Steffensen K.R., et al. Physiological differences between human and rat primary hepatocytes in response to liver X receptor activation by 3-[3-[N-(2-chloro-3-trifluoromethylbenzyl)-(2,2-diphenylethyl)amino]propyloxy]phe nylacetic acid hydrochloride (GW3965). Mol Pharmacol 72 4 (2007) 947-955
50. Schultz J.R., Tu H., Luk A., Repa J.J., Medina J.C., Li L., et al. Role of LXRs in control of lipogenesis. Genes Dev 14 22 (2000) 2831-2838
51. Grefhorst A., Elzinga B.M., Voshol P.J., Plosch T., Kok T., Bloks V.W., et al. Stimulation of lipogenesis by pharmacological activation of the liver X receptor leads to production of large, triglyceride-rich very low density lipoprotein particles. J Biol Chem 277 37 (2002) 34182-34190
52. Yoshikawa T., Shimano H., Amemiya-Kudo M., Yahagi N., Hasty A.H., Matsuzaka T., et al. Identification of liver X receptor-retinoid X receptor as an activator of the sterol regulatory element-binding protein 1c gene promoter. Mol Cell Biol 21 9 (2001) 2991-3000
53. Cozzone D., Debard C., Dif N., Ricard N., Disse E., Vouillarmet J., et al. Activation of liver X receptors promotes lipid accumulation but does not alter insulin action in human skeletal muscle cells. Diabetologia 49 5 (2006) 990-999
54. Choe S.S., Choi A.H., Lee J.W., Kim K.H., Chung J.J., Park J., et al. Chronic activation of liver X receptor induces beta-cell apoptosis through hyperactivation of lipogenesis: liver X receptor-mediated lipotoxicity in pancreatic beta-cells. Diabetes 56 6 (2007) 1534-1543
55. Repa J.J., Liang G., Ou J., Bashmakov Y., Lobaccaro J.M., Shimomura I., et al. Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta. Genes Dev 14 22 (2000) 2819-2830
56. Liang G., Yang J., Horton J.D., Hammer R.E., Goldstein J.L., and Brown M.S. Diminished hepatic response to fasting/refeeding and liver X receptor agonists in mice with selective deficiency of sterol regulatory element-binding protein-1c. J Biol Chem 277 11 (2002) 9520-9528
57. Joseph S.B., Laffitte B.A., Patel P.H., Watson M.A., Matsukuma K.E., Walczak R., et al. Direct and indirect mechanisms for regulation of fatty acid synthase gene expression by liver X receptors. J Biol Chem 277 13 (2002) 11019-11025
58. Chu K., Miyazaki M., Man W.C., and Ntambi J.M. Stearoyl-coenzyme A desaturase 1 deficiency protects against hypertriglyceridemia and increases plasma high-density lipoprotein cholesterol induced by liver X receptor activation. Mol Cell Biol 26 18 (2006) 6786-6798
59. Cha J.Y., and Repa J.J. The liver X receptor (LXR) and hepatic lipogenesis. The carbohydrate-response element-binding protein is a target gene of LXR. J Biol Chem 282 1 (2007) 743-751
60. Zhang Y., Repa J.J., Inoue Y., Hayhurst G.P., Gonzalez F.J., and Mangelsdorf D.J. Identification of a liver-specific uridine phosphorylase that is regulated by multiple lipid-sensing nuclear receptors. Mol Endocrinol 18 4 (2004) 851-862
61. Inaba T., Matsuda M., Shimamura M., Takei N., Terasaka N., Ando Y., et al. Angiopoietin-like protein 3 mediates hypertriglyceridemia induced by the liver X receptor. J Biol Chem 278 24 (2003) 21344-21351
62. Jakel H., Nowak M., Moitrot E., Dehondt H., Hum D.W., Pennacchio L.A., et al. The liver X receptor ligand T0901317 down-regulates APOA5 gene expression through activation of SREBP-1c. J Biol Chem 279 44 (2004) 45462-45469
63. Grefhorst A., van Dijk T.H., Hammer A., van der Sluijs F.H., Havinga R., Havekes L.M., et al. Differential effects of pharmacological liver X receptor activation on hepatic and peripheral insulin sensitivity in lean and ob/ob mice. Am J Physiol Endocrinol Metab 289 5 (2005) E829-E838
64. Albers M., Blume B., Schlueter T., Wright M.B., Kober I., Kremoser C., et al. A novel principle for partial agonism of liver X receptor ligands. Competitive recruitment of activators and repressors. J Biol Chem 281 8 (2006) 4920-4930
65. Herzog B., Hallberg M., Seth A., Woods A., White R., and Parker M.G. The nuclear receptor cofactor, receptor-interacting protein 140, is required for the regulation of hepatic lipid and glucose metabolism by liver X receptor. Mol Endocrinol 21 11 (2007) 2687-2697
66. Janowski B.A., Willy P.J., Devi T.R., Falck J.R., and Mangelsdorf D.J. An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature 383 6602 (1996) 728-731
67. Forman B.M., Ruan B., Chen J., Schroepfer Jr. G.J., and Evans R.M. The orphan nuclear receptor LXRalpha is positively and negatively regulated by distinct products of mevalonate metabolism. Proc Natl Acad Sci USA 94 20 (1997) 10588-10593
68. Janowski B.A., Grogan M.J., Jones S.A., Wisely G.B., Kliewer S.A., Corey E.J., et al. Structural requirements of ligands for the oxysterol liver X receptors LXRalpha and LXRbeta. Proc Natl Acad Sci USA 96 1 (1999) 266-271
69. Fu X., Menke J.G., Chen Y., Zhou G., MacNaul K.L., Wright S.D., et al. 27-hydroxycholesterol is an endogenous ligand for liver X receptor in cholesterol-loaded cells. J Biol Chem 276 42 (2001) 38378-38387
70. Quinet E.M., Savio D.A., Halpern A.R., Chen L., Miller C.P., and Nambi P. Gene-selective modulation by a synthetic oxysterol ligand of the liver X receptor. J Lipid Res 45 10 (2004) 1929-1942
71. Chen W., Chen G., Head D.L., Mangelsdorf D.J., and Russell D.W. Enzymatic reduction of oxysterols impairs LXR signaling in cultured cells and the livers of mice. Cell Metab 5 1 (2007) 73-79
72. Song C., Hiipakka R.A., and Liao S. Selective activation of liver X receptor alpha by 6alpha-hydroxy bile acids and analogs. Steroids 65 8 (2000) 423-427
73. Song C., and Liao S. Cholestenoic acid is a naturally occurring ligand for liver X receptor alpha. Endocrinology 141 11 (2000) 4180-4184
74. Lund E.G., Peterson L.B., Adams A.D., Lam M.H., Burton C.A., Chin J., et al. Different roles of liver X receptor alpha and beta in lipid metabolism: effects of an alpha-selective and a dual agonist in mice deficient in each subtype. Biochem Pharmacol 71 4 (2006) 453-463
75. Quinet E.M., Savio D.A., Halpern A.R., Chen L., Schuster G.U., Gustafsson J.A., et al. Liver X receptor (LXR)-beta regulation in LXRalpha-deficient mice: implications for therapeutic targeting. Mol Pharmacol 70 4 (2006) 1340-1349
76. Collins J.L., Fivush A.M., Watson M.A., Galardi C.M., Lewis M.C., Moore L.B., et al. Identification of a nonsteroidal liver X receptor agonist through parallel array synthesis of tertiary amines. J Med Chem 45 10 (2002) 1963-1966
77. Miao B., Zondlo S., Gibbs S., Cromley D., Hosagrahara V.P., Kirchgessner T.G., et al. Raising HDL cholesterol without inducing hepatic steatosis and hypertriglyceridemia by a selective LXR modulator. J Lipid Res 45 8 (2004) 1410-1417
78. Brunham L.R., Kruit J.K., Pape T.D., Parks J.S., Kuipers F., and Hayden M.R. Tissue-specific induction of intestinal ABCA1 expression with a liver X receptor agonist raises plasma HDL cholesterol levels. Circ Res 99 7 (2006) 672-674
79. Sparrow C.P., Baffic J., Lam M.H., Lund E.G., Adams A.D., Fu X., et al. A potent synthetic LXR agonist is more effective than cholesterol loading at inducing ABCA1 mRNA and stimulating cholesterol efflux. J Biol Chem 277 12 (2002) 10021-10027
80. Singh S.B., Ondeyka J.G., Liu W., Chen S., Chen T.S., Li X., et al. Discovery and development of dimeric podocarpic acid leads as potent agonists of liver X receptor with HDL cholesterol raising activity in mice and hamsters. Bioorg Med Chem Lett 15 11 (2005) 2824-2828
81. Kher S., Lake K., Sircar I., Pannala M., Bakir F., Zapf J., et al. 2-Aryl-N-acyl indole derivatives as liver X receptor (LXR) agonists. Bioorg Med Chem Lett 17 16 (2007) 4442-4446
82. Molteni V., Li X., Nabakka J., Liang F., Wityak J., Koder A., et al. N-acylthiadiazolines, a new class of liver X receptor agonists with selectivity for LXRbeta. J Med Chem 50 17 (2007) 4255-4259
83. Panday N., Benz J., Blum-Kaelin D., Bourgeaux V., Dehmlow H., Hartman P., et al. Synthesis and evaluation of anilinohexafluoroisopropanols as activators/modulators of LXRalpha and beta. Bioorg Med Chem Lett 16 19 (2006) 5231-5237
84. Traves P.G., Hortelano S., Zeini M., Chao T.H., Lam T., Neuteboom S.T., et al. Selective activation of liver X receptors by acanthoic acid-related diterpenes. Mol Pharmacol 71 6 (2007) 1545-1553
85. Szewczyk J.W., Huang S., Chin J., Tian J., Mitnaul L., Rosa R.L., et al. SAR studies: designing potent and selective LXR agonists. Bioorg Med Chem Lett 16 11 (2006) 3055-3060
86. Tamehiro N., Sato Y., Suzuki T., Hashimoto T., Asakawa Y., Yokoyama S., et al. Riccardin C: a natural product that functions as a liver X receptor (LXR)alpha agonist and an LXRbeta antagonist. FEBS Lett 579 24 (2005) 5299-5304
87. Ou J., Tu H., Shan B., Luk A., DeBose-Boyd R.A., Bashmakov Y., et al. Unsaturated fatty acids inhibit transcription of the sterol regulatory element-binding protein-1c (SREBP-1c) gene by antagonizing ligand-dependent activation of the LXR. Proc Natl Acad Sci USA 98 11 (2001) 6027-6032
88. Yoshikawa T., Shimano H., Yahagi N., Ide T., Amemiya-Kudo M., Matsuzaka T., et al. Polyunsaturated fatty acids suppress sterol regulatory element-binding protein 1c promoter activity by inhibition of liver X receptor (LXR) binding to LXR response elements. J Biol Chem 277 3 (2002) 1705-1711
89. Song C., Hiipakka R.A., and Liao S. Auto-oxidized cholesterol sulfates are antagonistic ligands of liver X receptors: implications for the development and treatment of atherosclerosis. Steroids 66 6 (2001) 473-479
90. Kim K.H., Choi S.H., Lee T.S., Oh W.K., Kim D.S., and Kim J.B. Selective LXRalpha inhibitory effects observed in plant extracts of MEH184 (Parthenocissua tricuspidata) and MEH185 (Euscaphis japonica). Biochem Biophys Res Commun 349 2 (2006) 513-518
91. Tangirala R.K., Bischoff E.D., Joseph S.B., Wagner B.L., Walczak R., Laffitte B.A., et al. Identification of macrophage liver X receptors as inhibitors of atherosclerosis. Proc Natl Acad Sci USA 99 18 (2002) 11896-11901
92. Levin N., Bischoff E.D., Daige C.L., Thomas D., Vu C.T., Heyman R.A., et al. Macrophage liver X receptor is required for antiatherogenic activity of LXR agonists. Arterioscler Thromb Vasc Biol 25 1 (2005) 135-142
93. Bradley M.N., Hong C., Chen M., Joseph S.B., Wilpitz D.C., Wang X., et al. Ligand activation of LXR beta reverses atherosclerosis and cellular cholesterol overload in mice lacking LXR alpha and apoE. J Clin Invest 117 8 (2007) 2337-2346
94. Castrillo A., Joseph S.B., Marathe C., Mangelsdorf D.J., and Tontonoz P. Liver X receptor-dependent repression of matrix metalloproteinase-9 expression in macrophages. J Biol Chem 278 12 (2003) 10443-10449
95. Terasaka N., Hiroshima A., Ariga A., Honzumi S., Koieyama T., Inaba T., et al. Liver X receptor agonists inhibit tissue factor expression in macrophages. FEBS J 272 6 (2005) 1546-1556
96. Ogawa D., Stone J.F., Takata Y., Blaschke F., Chu V.H., Towler D.A., et al. Liver X receptor agonists inhibit cytokine-induced osteopontin expression in macrophages through interference with activator protein-1 signaling pathways. Circ Res 96 7 (2005) e59-e67
97. Fontaine C., Rigamonti E., Nohara A., Gervois P., Teissier E., Fruchart J.C., et al. Liver X receptor activation potentiates the lipopolysaccharide response in human macrophages. Circ Res 101 1 (2007) 40-49
98. Arai S., Shelton J.M., Chen M., Bradley M.N., Castrillo A., Bookout A.L., et al. A role for the apoptosis inhibitory factor AIM/Spalpha/Api6 in atherosclerosis development. Cell Metab 1 3 (2005) 201-213
99. Valledor A.F., Hsu L.C., Ogawa S., Sawka-Verhelle D., Karin M., and Glass C.K. Activation of liver X receptors and retinoid X receptors prevents bacterial-induced macrophage apoptosis. Proc Natl Acad Sci USA 101 51 (2004) 17813-17818