Synthetic LXR agonist attenuates plaque formation in apoE-/-mice without inducing liver steatosis and hypertriglyceridemia

Journal of Lipid Research

Volumn 50, Issue 2, 2009, Pages 312-326

  Kratzer, Adelheid ^a,b   Buchebner, Marlene ^a   Pfeifer, Thomas ^a   Becker, Tatjana M ^a   Uray, Georg ^c   Miyazaki, Makoto ^a   Miyazaki Anzai, Shinobu ^a   Ebner, Birgit ^a   Chandak, Prakash G ^a   Kadam, Rajendra S ^b   Calayir, Emine ^a   Rathke, Nora ^a   Ahammer, Helmut ^a   Radovic, Branislav ^a   Trauner, Michael ^a   Hoefler, Gerald ^a   Kompella, Uday B ^b   Fauler, Guenter ^a   Levi, Moshe ^b   Levak Frank, Sanja ^a   Kostner, Gerhard M ^a   Kratky, Dagmar ^a   more..

^a MEDICAL UNIVERSITY OF GRAZ   (Austria)

^b UNIVERSITY OF COLORADO   (United States)

^c UNIVERSITY OF GRAZ   (Austria)

Author keywords

ABC transporter; Atherogenesis; Cholesterol catabolism; Gene expression; Liver X receptor

Indexed keywords

ABC TRANSPORTER A1; ABC TRANSPORTER G1; APOLIPOPROTEIN E; CHOLESTEROL 7ALPHA MONOOXYGENASE; LIVER X RECEPTOR AGONIST; MESSENGER RNA; N (2,2,2 TRIFLUOROETHYL) N [4 [2,2,2 TRIFLUORO 1 HYDROXY 1 (TRIFLUOROMETHOXY)ETHYL]PHENYL]BENZENESULFONAMIDE; N,N DIMETHYL 3BETA HYDROXYCHOLENAMIDE; STEROL REGULATORY ELEMENT BINDING PROTEIN 1C; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; ABC TRANSPORTER; CELL RECEPTOR; CHOLIC ACID DERIVATIVE; DNA BINDING PROTEIN; LIVER X RECEPTOR; N,N DIMETHYL 3 HYDROXY 5 CHOLENAMIDE; N,N-DIMETHYL-3-HYDROXY-5-CHOLENAMIDE; STEROL REGULATORY ELEMENT BINDING PROTEIN 1;

ANIMAL CELL; ANIMAL CELL CULTURE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ATHEROSCLEROSIS; ATHEROSCLEROTIC PLAQUE; CELL FRACTIONATION; CONTROLLED STUDY; DIETARY INTAKE; DRUG MECHANISM; FATTY LIVER; FEMALE; HISTOPATHOLOGY; HYPERTRIGLYCERIDEMIA; IMMUNOBLOTTING; INTESTINE; LIVER; MACROPHAGE; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; REAL TIME POLYMERASE CHAIN REACTION; REGULATORY MECHANISM; RNA ISOLATION; ANIMAL; C57BL MOUSE; CHEMICALLY INDUCED DISORDER; DRUG POTENTIATION; FOAM CELL; GENETICS; METABOLISM; PATHOLOGY; TIME; TRANSGENIC MOUSE;

ANIMALS; APOLIPOPROTEINS E; ATHEROSCLEROSIS; ATP-BINDING CASSETTE TRANSPORTERS; CHOLIC ACIDS; DNA-BINDING PROTEINS; FATTY LIVER; FEMALE; FOAM CELLS; HYPERTRIGLYCERIDEMIA; MACROPHAGES; MALE; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; RECEPTORS, CYTOPLASMIC AND NUCLEAR; RNA, MESSENGER; STEROL REGULATORY ELEMENT BINDING PROTEIN 1; TIME FACTORS;

EID: 64749108682     PISSN: 00222275     EISSN: 15397262     Source Type: Journal    
DOI: 10.1194/jlr.M800376-JLR200     Document Type: Article

References (38)

1. Janowski, B. A., P. J. Willy, T. R. Devi, J. R. Falck, and D. J. Mangelsdorf. 1996. An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature. 383: 728-731.
2. Costet, P., Y. Luo, N. Wang, and A. R. Tall. 2000. Sterol-dependent transactivation of the ABC1 promoter by the liver X receptor/retinoid X receptor. J. Biol. Chem. 275: 28240-28245.
3. Repa, J. J., S. D. Turley, J. A. Lobaccaro, J. Medina, L. Li, K. Lustig, B. Shan, R. A. Heyman, J. M. Dietschy, and D. J. Mangelsdorf. 2000. Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers. Science. 289: 1524-1529.
4. Schwartz, K., R. M. Lawn, and D. P. Wade. 2000. ABC1 gene expression and apoA-I-mediated cholesterol efflux are regulated by LXR. Biochem. Biophys. Res. Commun. 274: 794-802.
5. Venkateswaran, A., J. J. Repa, J. M. Lobaccaro, A. Bronson, D. J. Mangelsdorf, and P. A. Edwards. 2000. Human white/murine ABC8 mRNA levels are highly induced in lipid-loaded macrophages. A transcriptional role for specific oxysterols. J. Biol. Chem. 275: 14700-14707.
6. Venkateswaran, A., B. A. Laffitte, S. B. Joseph, P. A. Mak, D. C. Wilpitz, P. A. Edwards, and P. Tontonoz. 2000. Control of cellular cholesterol efflux by the nuclear oxysterol receptor LXR alpha. Proc. Natl. Acad. Sci. USA. 97: 12097-12102.
7. Brunham, L. R., J. K. Kruit, T. D. Pape, J. S. Parks, F. Kuipers, and M. R. Hayden. 2006. Tissue-specific induction of intestinal ABCA1 expression with a liver X receptor agonist raises plasma HDL cholesterol levels. Circ. Res. 99: 672-674.
8. Repa, J. J., K. E. Berge, C. Pomajzl, J. A. Richardson, H. Hobbs, and D. J. Mangelsdorf. 2002. Regulation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 by the liver X receptors alpha and beta. J. Biol. Chem. 277: 18793-18800.
9. Repa, J. J., G. Liang, J. Ou, Y. Bashmakov, J. M. Lobaccaro, I. Shimomura, B. Shan, M. S. Brown, J. L. Goldstein, and D. J. Mangelsdorf. 2000. Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta. Genes Dev. 14: 2819-2830.
10. Yoshikawa, T., H. Shimano, M. Amemiya-Kudo, N. Yahagi, A. H. Hasty, T. Matsuzaka, H. Okazaki, Y. Tamura, Y. Iizuka, K. Ohashi, et al. 2001. 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: 2991-3000.
11. Zhang, Y., J. J. Repa, K. Gauthier, and D. J. Mangelsdorf. 2001. Regulation of lipoprotein lipase by the oxysterol receptors, LXRalpha and LXRbeta. J. Biol. Chem. 276: 43018-43024.
12. Joseph, S. B.,B. A. Laffitte, P. H. Patel, M. A. Watson,K. E. Matsukuma, R. Walczak, J. L. Collins, T. F. Osborne, and P. Tontonoz. 2002. Direct and indirect mechanisms for regulation of fatty acid synthase gene expression by liver X receptors. J. Biol. Chem. 277: 11019-11025.
13. Chu, K., M. Miyazaki, W. C. Man, and J. M. Ntambi. 2006. Stearoylcoenzyme A desaturase 1 deficiency protects against hypertriglyceridemia and increases plasma high-density lipoprotein cholesterol induced by liver X receptor activation. Mol. Cell. Biol. 26: 6786-6798.
14. Cha, J. Y., and J. J. Repa. 2007. The liver X receptor (LXR) and hepatic lipogenesis. The carbohydrate-response element-binding protein is a target gene of LXR. J. Biol. Chem. 282: 743-751.
15. Lehmann, J. M., S. A. Kliewer, L. B. Moore, T. A. Smith-Oliver, B. B. Oliver, J. L. Su, S. S. Sundseth, D. A. Winegar, D. E. Blanchard, T. A. Spencer, et al. 1997. Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway. J. Biol. Chem. 272: 3137-3140.
16. Joseph, S. B., E. McKilligin, L. Pei, M. A. Watson, A. R. Collins, B. A. Laffitte, M. Chen, G. Noh, J. Goodman, G. N. Hagger, et al. 2002. Synthetic LXR ligand inhibits the development of atherosclerosis in mice. Proc. Natl. Acad. Sci. USA. 99: 7604-7609.
17. Terasaka, N., A. Hiroshima, T. Koieyama, N. Ubukata, Y. Morikawa, D. Nakai, and T. Inaba. 2003. T-0901317, a synthetic liver X receptor ligand, inhibits development of atherosclerosis in LDL receptor-deficient mice. FEBS Lett. 536: 6-11.
18. Quinet, E. M., D. A. Savio, A. R. Halpern, L. Chen, C. P. Miller, and P. Nambi. 2004. Gene-selective modulation by a synthetic oxysterol ligand of the liver X receptor. J. Lipid Res. 45: 1929-1942.
19. Louw, D. F., G. Strating, and H. J. Backer. 1954. Delta-5-Steroids and provitamins D with branched side chains. III. Preparation and reduction of some delta-5-steroid omega-amines. Recueil des Travaux Chimiques des Pays-Bas et de la Belgique. 73: 667-676.
20. Wang, X., R. Sato, M. S. Brown, X. Hua, and J. L. Goldstein. 1994. SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis. Cell. 77: 53-62.
21. Lowry, O. H., N. J. Rosebrough, A. L. Farr, and R. J. Randall. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193: 265-275.
22. Miyazaki, M., H. J. Kim, W. C. Man, and J. M. Ntambi. 2001. Oleoyl-CoA is the major de novo product of stearoyl-CoA desaturase 1 gene isoform and substrate for the biosynthesis of the Harderian gland 1-alkyl-2,3-diacylglycerol. J. Biol. Chem. 276: 39455-39461.
23. Pfaffl, M. W., G. W. Horgan, and L. Dempfle. 2002. Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res. 30: e36.
24. Repa, J. J., and D. J. Mangelsdorf. 2000. The role of orphan nuclear receptors in the regulation of cholesterol homeostasis. Annu. Rev. Cell Dev. Biol. 16: 459-481.
25. Schultz, J. R., H. Tu, A. Luk, J. J. Repa, J. C. Medina, L. Li, S. Schwendner, S. Wang, M. Thoolen, D. J. Mangelsdorf, et al. 2000. Role of LXRs in control of lipogenesis. Genes Dev. 14: 2831-2838.
26. Uyeda, K., and J. J. Repa. 2006. Carbohydrate response element binding protein, ChREBP, a transcription factor coupling hepatic glucose utilization and lipid synthesis. Cell Metab. 4: 107-110.
27. Yamashita, H., M. Takenoshita, M. Sakurai, R. K. Bruick, W. J. Henzel, W. Shillinglaw, D. Arnot, and K. Uyeda. 2001. A glucose-responsive transcription factor that regulates carbohydrate metabolism in the liver. Proc. Natl. Acad. Sci. USA. 98: 9116-9121.
28. Mitro, N., L. Vargas, R. Romeo, A. Koder, and E. Saez. 2007. T0901317 is a potent PXR ligand: implications for the biology ascribed to LXR. FEBS Lett. 581: 1721-1726.
29. Bradley, M. N., C. Hong, M. Chen, S. B. Joseph, D. C. Wilpitz, X. Wang, A. J. Lusis, A. Collins, W. A. Hseuh, J. L. Collins, et al. 2007. Ligand activation of LXR beta reverses atherosclerosis and cellular cholesterol overload in mice lacking LXR alpha and apoE. J. Clin. Invest. 117: 2337-2346.
30. Schmidt, R. J., J. V. Ficorilli, Y. Zhang, K. S. Bramlett, T. P. Beyer, K. Borchert, M. S. Dowless, K. A. Houck, T. P. Burris, P. I. Eacho, et al. 2006. A 15-ketosterol is a liver X receptor ligand that suppresses sterol-responsive element binding protein-2 activity. J. Lipid Res. 47: 1037-1044.
31. Oram, J. F., R. M. Lawn, M. R. Garvin, and D. P. Wade. 2000. ABCA1 is the cAMP-inducible apolipoprotein receptor that mediates cholesterol secretion from macrophages. J. Biol. Chem. 275: 34508-34511.
32. Oram, J. F., and A. M. Vaughan. 2000. ABCA1-mediated transport of cellular cholesterol and phospholipids to HDL apolipoproteins. Curr. Opin. Lipidol. 11: 253-260.
33. Klucken, J., C. Buchler, E. Orso, W. E. Kaminski, M. Porsch-Ozcurumez, G. Liebisch, M. Kapinsky, W. Diederich, W. Drobnik, M. Dean, et al. 2000. ABCG1 (ABC8), the human homolog of the Drosophila white gene, is a regulator of macrophage cholesterol and phospholipid transport. Proc. Natl. Acad. Sci. USA. 97: 817-822.
34. Lee, M. H., K. Lu, S. Hazard, H. Yu, S. Shulenin, H. Hidaka, H. Kojima, R. Allikmets, N. Sakuma, R. Pegoraro, et al. 2001. Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption. Nat. Genet. 27: 79-83.
35. Berge, K. E., H. Tian, G. A. Graf, L. Yu, N. V. Grishin, J. Schultz, P. Kwiterovich, B. Shan, R. Barnes, and H. H. Hobbs. 2000. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science. 290: 1771-1775.
36. Murthy, S., E. Born, S. N. Mathur, and F. J. Field. 2002. LXR/RXR activation enhances basolateral efflux of cholesterol in CaCo-2 cells. J. Lipid Res. 43: 1054-1064.
37. Tang, W., Y. Ma, L. Jia, Y. A. Ioannou, J. P. Davies, and L. Yu. 2008. Niemann-Pick C1-like 1 is required for an LXR agonist to raise plasma HDL cholesterol in mice. Arterioscler. Thromb. Vasc. Biol. 28: 448-454.
38. Davis, H. R., and E. P. Veltri. 2007. Zetia: inhibition of Niemann-Pick C1 Like 1 (NPC1L1) to reduce intestinal cholesterol absorption and treat hyperlipidemia. J. Atheroscler. Thromb. 14: 99-108.