Low dose of the liver X receptor agonist, AZ876, reduces atherosclerosis in APOE*3Leiden mice without affecting liver or plasma triglyceride levels

British Journal of Pharmacology

Volumn 162, Issue 7, 2011, Pages 1553-1563

  Van Der Hoorn, J W A ^a,b   Linden D ^c   Lindahl, U ^c   Bekkers, M E A ^a   Voskuilen, M ^a   Nilsson, R ^c   Oscarsson, J ^c   Lindstedt, E L ^c   Princen, H M G ^a  

^a TNO   (Netherlands)

^b LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

^c ASTRAZENECA R AND D   (Sweden)

Author keywords

inflammation; lipids; reverse cholesterol transport

Indexed keywords

3 [3 [[2 CHLORO 3 (TRIFLUOROMETHYL)BENZYL](2 DIPHENYLETHYL)AMINO]PROPOXY]PHENYLACETIC ACID; ABC TRANSPORTER A1; ALANINE AMINOTRANSFERASE; APOLIPOPROTEIN E3; AZ 876; BILE ACID; CHOLESTEROL; CHOLESTEROL ESTER; LANOSTEROL; LIPID; LIVER X RECEPTOR AGONIST; LIVER X RECEPTOR ALPHA; LIVER X RECEPTOR BETA; TRIACYLGLYCEROL; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIINFLAMMATORY ACTIVITY; ARTICLE; ATHEROGENIC DIET; ATHEROSCLEROSIS; BINDING SITE; BODY WEIGHT; CHOLESTEROL BLOOD LEVEL; CHOLESTEROL SYNTHESIS; CHOLESTEROL TRANSPORT; CONTROLLED STUDY; DISEASE COURSE; DISEASE SEVERITY; DOSE RESPONSE; DRUG DOSE INCREASE; DRUG MEGADOSE; DRUG STRUCTURE; FATTY LIVER; FEMALE; FOOD INTAKE; HISTOCHEMISTRY; HISTOPATHOLOGY; HYPERTRIGLYCERIDEMIA; IMMUNOHISTOCHEMISTRY; INFLAMMATION; LIGAND BINDING; LIPID BLOOD LEVEL; LOW DRUG DOSE; MALE; MOUSE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; TRIACYLGLYCEROL BLOOD LEVEL;

ANILINE COMPOUNDS; ANIMALS; APOLIPOPROTEIN E3; ATHEROSCLEROSIS; BENZOIC ACIDS; BENZYLAMINES; CHOLESTEROL; CYTOKINES; DOSE-RESPONSE RELATIONSHIP, DRUG; FATTY LIVER; FEMALE; HUMANS; HYPERTRIGLYCERIDEMIA; INFLAMMATION; LIPID METABOLISM; LIPIDS; LIVER; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; ORPHAN NUCLEAR RECEPTORS; THIAZOLES; TRIGLYCERIDES;

EID: 79952378989     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2010.01168.x     Document Type: Article

References (41)

1. Alexander SPH, Mathie A, Peters JA, (2009). Guide to receptors and channels (GRAC), 4th edn. Br J Pharmacol 158 (Suppl. 1): S1-S254.
2. Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, et al. (2005). Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 366: 1267-1278.
3. Bjorkhem I, Miettinen T, Reihner E, Ewerth S, Angelin B, Einarsson K, (1987). Correlation between serum levels of some cholesterol precursors and activity of HMG-CoA reductase in human liver. J Lipid Res 28: 1137-1143. (Pubitemid 17151579)
4. Boström J, Brickmann K, Broo A, Holm P, Li L, Sandberg P, et al. (2006). Derivatives of isothiazol-3(2H)-one 1,1-dioxides as liver X receptor modulators. (WO2006073363).
5. Brunham LR, Kruit JK, Iqbal J, Fievet C, Timmins JM, Pape TD, et al. (2006). Intestinal ABCA1 directly contributes to HDL biogenesis in vivo. J Clin Invest 116: 1052-1062.
6. Collins JL, Fivush AM, Watson MA, Galardi CM, Lewis MC, Moore LB, et al. (2002). Identification of a nonsteroidal liver X receptor agonist through parallel array synthesis of tertiary amines. J Med Chem 45: 1963-1966. (Pubitemid 34477709)
7. Dai X, Ou X, Hao X, Cao D, Tang Y, Hu Y, et al. (2007). Effect of T0901317 on hepatic proinflammatory gene expression in apoE-/- mice fed a high-fat/high-cholesterol diet. Inflammation 30: 105-117. (Pubitemid 46985775)
8. Delsing DJ, Offerman EH, van Duyvenvoorde W, van der Boom H, de Wit EC, Gijbels MJ, et al. (2001). Acyl-CoA:cholesterol acyltransferase inhibitor avasimibe reduces atherosclerosis in addition to its cholesterol-lowering effect in ApoE*3-Leiden mice. Circulatio 103: 1778-1786. (Pubitemid 32291416)
9. Delsing DJ, Jukema JW, Van De Wiel MA, Emeis JJ, van der Laarse A, Havekes LM, et al. (2003). Differential effects of amlodipine and atorvastatin treatment and their combination on atherosclerosis in apoE*3-Leiden transgenic mice. J Cardiovasc Pharmacol 42: 63-70. (Pubitemid 36791351)
10. Folch J, Lees M, Sloane Stanley GH, (1957). A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226: 497-509.
11. Grefhorst A, Elzinga BM, Voshol PJ, Plosch T, Kok T, Bloks VW, et al. (2002). 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: 34182-34190.
12. Groot PH, Pearce NJ, Yates JW, Stocker C, Sauermelch C, Doe CP, et al. (2005). Synthetic LXR agonists increase LDL in CETP species. J Lipid Res 46: 2182-2191. (Pubitemid 41377470)
13. Gruen ML, Plummer MR, Zhang W, Posey KA, Linton MF, Fazio S, et al. (2005). Persistence of high density lipoprotein particles in obese mice lacking apolipoprotein A-I. J Lipid Res 46: 2007-2014. (Pubitemid 41248498)
14. van der Hoorn JW, Kleemann R, Havekes LM, Kooistra T, Princen HM, Jukema JW, (2007). Olmesartan and pravastatin additively reduce development of atherosclerosis in APOE*3Leiden transgenic mice. J Hypertens 25: 2454-2462. (Pubitemid 350060384)
15. Janowski BA, Willy PJ, Devi TR, Falck JR, Mangelsdorf DJ, (1996). An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature 383: 728-731. (Pubitemid 26360651)
16. Jiang XC, Agellon LB, Walsh A, Breslow JL, Tall A, (1992). Dietary cholesterol increases transcription of the human cholesteryl ester transfer protein gene in transgenic mice. Dependence on natural flanking sequences. J Clin Invest 90: 1290-1295.
17. Joseph SB, McKilligin E, Pei L, Watson MA, Collins AR, Laffitte BA, et al. (2002). Synthetic LXR ligand inhibits the development of atherosclerosis in mice. Proc Natl Acad Sci USA 99: 7604-7609. (Pubitemid 34568738)
18. Kleemann R, Princen HM, Emeis JJ, Jukema JW, Fontijn RD, Horrevoets AJ, et al. (2003). Rosuvastatin reduces atherosclerosis development beyond and independent of its plasma cholesterol-lowering effect in APOE*3-Leiden transgenic mice: evidence for antiinflammatory effects of rosuvastatin. Circulation 108: 1368-1374. (Pubitemid 37174416)
19. Kooistra T, Verschuren L, de Vries-Van der Weij J, Koenig W, Toet K, Princen HM, et al. (2006). Fenofibrate reduces atherogenesis in ApoE*3Leiden mice: evidence for multiple antiatherogenic effects besides lowering plasma cholesterol. Arterioscler Thromb Vasc Biol 26: 2322-2330. (Pubitemid 44465729)
20. Kratzer A, Buchebner M, Pfeifer T, Becker TM, Uray G, Miyazaki M, et al. (2009). Synthetic LXR agonist attenuates plaque formation in apoE-/- mice without inducing liver steatosis and hypertriglyceridemia. J Lipid Res 50: 312-326.
21. Libby P, (2002). Inflammation in atherosclerosis. Nature 420: 868-874. (Pubitemid 36019640)
22. Lu TT, Repa JJ, Mangelsdorf DJ, (2001). Orphan nuclear receptors as eLiXiRs and FiXeRs of sterol metabolism. J Biol Chem 276: 37735-37738.
23. Miao B, Zondlo S, Gibbs S, Cromley D, Hosagrahara VP, Kirchgessner TG, et al. (2004). Raising HDL cholesterol without inducing hepatic steatosis and hypertriglyceridemia by a selective LXR modulator. J Lipid Res 45: 1410-1417. (Pubitemid 39006968)
24. Naik SU, Wang X, Da Silva JS, Jaye M, Macphee CH, Reilly MP, et al. (2006). Pharmacological activation of liver X receptors promotes reverse cholesterol transport in vivo. Circulation 113: 90-97. (Pubitemid 43958493)
25. Nilsson R, Iöfgren L, Hansson GI, (2009). Automated extraction and analysis of plasma biomarkers for cholesterol absorbtion, cholesterol synthesis and synthesis of bile acids by HPLC-APPI tandem mass spectrometry.
26. Quinet EM, Basso MD, Halpern AR, Yates DW, Steffan RJ, Clerin V, et al. (2009). LXR ligand lowers LDL cholesterol in primates, is lipid neutral in hamster, and reduces atherosclerosis in mouse. J Lipid Res 50: 2358-2370.
27. Rader DJ, (2007). Liver X receptor and farnesoid X receptor as therapeutic targets. Am J Cardiol 100: n15-n19.
28. Repa JJ, Mangelsdorf DJ, (2000). The role of orphan nuclear receptors in the regulation of cholesterol homeostasis. Annu Rev Cell Dev Biol 16: 459-481. (Pubitemid 32037514)
29. Repa JJ, Liang G, Ou J, Bashmakov Y, Lobaccaro JM, Shimomura I, et al. (2000). Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta. Genes Dev 14: 2819-2830.
30. Rigamonti E, Chinetti-Gbaguidi G, Staels B, (2008). Regulation of macrophage functions by PPAR-alpha, PPAR-gamma, and LXRs in mice and men. Arterioscler Thromb Vasc Biol 28: 1050-1059.
31. Schultz JR, Tu H, Luk A, Repa JJ, Medina JC, Li L, et al. (2000). Role of LXRs in control of lipogenesis. Genes Dev 14: 2831-2838.
32. Tall AR, (2008). Cholesterol efflux pathways and other potential mechanisms involved in the athero-protective effect of high density lipoproteins. J Intern Med 263: 256-273. (Pubitemid 351207349)
33. Tang W, Ma Y, Jia L, Ioannou YA, Davies JP, Yu L, (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.
34. Terasaka N, Hiroshima A, Koieyama T, Ubukata N, Morikawa Y, Nakai D, et al. (2003). T-0901317, a synthetic liver X receptor ligand, inhibits development of atherosclerosis in LDL receptor-deficient mice. FEBS Lett 536: 6-11. (Pubitemid 36206397)
35. Verschuren L, Kleemann R, Offerman EH, Szalai AJ, Emeis SJ, Princen HM, et al. (2005). Effect of low dose atorvastatin versus diet-induced cholesterol lowering on atherosclerotic lesion progression and inflammation in apolipoprotein E*3-Leiden transgenic mice. Arterioscler Thromb Vasc Biol 25: 161-167. (Pubitemid 40054270)
36. Verschuren L, de Vries-Van der Weij J, Zadelaar S, Kleemann R, Kooistra T, (2009). LXR agonist suppresses atherosclerotic lesion growth and promotes lesion regression in apoE*3Leiden mice: time course and mechanisms. J Lipid Res 50: 301-311.
37. van Vlijmen BJ, van den Maagdenberg AM, Gijbels MJ, van der Boom H, HogenEsch H, Frants RR, et al. (1994). Diet-induced hyperlipoproteinemia and atherosclerosis in apolipoprotein E3-Leiden transgenic mice. J Clin Invest 93: 1403-1410. (Pubitemid 24116375)
38. Wang Y, Rogers PM, Su C, Varga G, Stayrook KR, Burris TP, (2008). Regulation of cholesterologenesis by the oxysterol receptor, LXRalpha. J Biol Chem 283: 26332-26339.
39. Westerterp M, van der Hoogt CC, de Haan W, Offerman EH, Dallinga-Thie GM, Jukema JW, et al. (2006). Cholesteryl ester transfer protein decreases high-density lipoprotein and severely aggravates atherosclerosis in APOE*3-Leiden mice. Arterioscler Thromb Vasc Biol 26: 2552-2559. (Pubitemid 44607480)
40. Zadelaar S, Kleemann R, Verschuren L, de Vries-Van der Weij J, van der Hoorn JW, Princen HM, et al. (2007). Mouse models for atherosclerosis and pharmaceutical modifiers. Arterioscler Thromb Vasc Biol 27: 1706-1721. (Pubitemid 47207165)
41. Zelcer N, Tontonoz P, (2006). Liver X receptors as integrators of metabolic and inflammatory signalling. J Clin Invest 116: 607-614. (Pubitemid 43326865)