Enhanced Synthesis of the Oxysterol 24(S),25-Epoxycholesterol in Macrophages by Inhibitors of 2,3-Oxidosqualene: Lanosterol Cyclase - A Novel Mechanism for the Attenuation of Foam Cell Formation

Circulation Research

Volumn 93, Issue 8, 2003, Pages 717-725

  Rowe, Andrea H ^a,b   Argmann, Carmen A ^a,b   Edwards, Jane Y ^a,b   Sawyez, Cynthia G ^a,b   Morand, Olivier H ^c   Hegele, Robert A ^a,b   Huff, Murray W ^a,b  

^a ROBARTS RESEARCH INSTITUTE   (Canada)

^b UNIVERSITY OF WESTERN ONTARIO   (Canada)

^c F HOFFMANN LA ROCHE LTD   (Switzerland)

Author keywords

ATP binding cassette A1; Liver X receptors; Oxidosqualene:lanosterol cyclase; Oxysterols; SREBP 1

Indexed keywords

ABC TRANSPORTER; ATP BINDING CASSETTE A1; ATP BINDING CASSETTE G1; CHOLESTEROL DERIVATIVE; CHOLESTEROL ESTER; ENZYME INHIBITOR; LANOSTEROL SYNTHASE INHIBITOR; LIVER X RECEPTOR; LOW DENSITY LIPOPROTEIN RECEPTOR; OXYSTEROL 24,25 EPOXYCHOLESTEROL; RECEPTOR; STEROL REGULATORY ELEMENT BINDING PROTEIN; STEROL REGULATORY ELEMENT BINDING PROTEIN 1; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; VERY LOW DENSITY LIPOPROTEIN; 24,25 EPOXYCHOLESTEROL; 24,25-EPOXYCHOLESTEROL; ABC TRANSPORTER A1; ABCG1 PROTEIN, HUMAN; CELL RECEPTOR; CHOLESTEROL; DRUG DERIVATIVE; LANOSTEROL SYNTHASE; LIPOPROTEIN LIPASE; MESSENGER RNA; MUTASE; VERY LOW DENSITY LIPOPROTEIN TRIGLYCERIDE;

ANIMAL CELL; ARTICLE; ATHEROGENESIS; ATHEROSCLEROSIS; CHOLESTEROL SYNTHESIS; CONTROLLED STUDY; ENZYME INHIBITION; FOAM CELL; GENE EXPRESSION; HUMAN; HUMAN CELL; HYPERTRIGLYCERIDEMIA; HYPOTHESIS; LIPID METABOLISM; MACROPHAGE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PROCESSING; UPREGULATION; ANIMAL; BIOSYNTHESIS; CELL CULTURE; CELL LINE; DRUG ANTAGONISM; DRUG EFFECT; ENZYMOLOGY; GENETICS; HYPERLIPOPROTEINEMIA TYPE 4; METABOLISM;

ANIMALS; ATP-BINDING CASSETTE TRANSPORTERS; CELL LINE; CELLS, CULTURED; CHOLESTEROL; CHOLESTEROL ESTERS; ENZYME INHIBITORS; FOAM CELLS; HUMANS; HYPERLIPOPROTEINEMIA TYPE IV; INTRAMOLECULAR TRANSFERASES; LIPID METABOLISM; LIPOPROTEIN LIPASE; LIPOPROTEINS, VLDL; MACROPHAGES; MICE; RECEPTORS, CYTOPLASMIC AND NUCLEAR; RECEPTORS, LDL; RNA, MESSENGER; TRIGLYCERIDES;

EID: 0142120095     PISSN: 00097330     EISSN: None     Source Type: Journal    
DOI: 10.1161/01.RES.0000097606.43659.F4     Document Type: Article

References (30)

1. Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med. 1999;340:115-126.
2. Tall AR, Costet P, Wang N. Regulation and mechanisms of macrophage cholesterol efflux. J Clin Invest. 2002;110:899-904.
3. Attie AD, Kastelein JP, Hayden MR. Pivotal role of ABCA1 in reverse cholesterol transport influencing HDL levels and susceptibility to atherosclerosis. J Lipid Res. 2001;42:1717-1726.
4. Francis GA, Knopp RH, Oram JF. Defective removal of cellular cholesterol and phospholipids by apolipoprotein A-I in Tangier disease. J Clin Invest. 1995;96:78-87.
5. Oram JF. ATP-binding cassette transporter A1 and cholesterol trafficking. Curr Opin Lipidol. 2002;13:373-381.
6. Repa JJ, Mangelsdorf DJ. The liver X receptor gene team: potential new players in atherosclerosis. Nat Med. 2002;8:1243-1248.
7. Francis GA, Annicotte JS, Auwerx J. Liver X receptors: Xcreting Xol to combat atherosclerosis. Trends Mol Med. 2002;8:455-458.
8. Horton JD, Goldstein JL, Brown MS. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest. 2002;109:1125-1131.
9. Lehmann JM, Kliewer SA, Moore LB, Smith-Oliver TA, Oliver BB, Su JL, Sundseth SS, Winegar DA, Blanchard DE, Spencer TA, Willson TM. Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway. J Biol Chem. 1997;272:3137-3140.
10. Fu X, Menke JG, Chen Y, Zhou G, Macnaul KL, Wright SD, Sparrow CP, Lund EG. 27-Hydroxycholesterol is an endogenous ligand for liver X receptor in cholesterol-loaded cells. J Biol Chem. 2001;276:38378-38387.
11. Sparrow CP, Baffic J, Lam MH, Lund EG, Adams AD, Fu X, Hayes N, Jones AB, Macnaul KL, Ondeyka J, Singh S, Wang J, Zhou G, Moller DE, Wright SD, Menke JG. A potent synthetic LXR agonist is more effective than cholesterol loading at inducing ABCAI mRNA and stimulating cholesterol efflux. J Biol Chem. 2002;277:10021-10027.
12. Nelson JA, Steckbeck SR, Spencer TA. Biosynthesis of 24,25-epoxycholesterol from squalene 2,3;22,23-dioxide. J Biol Chem. 1981;256:1067-1068.
13. Morand OH, Aebi JD, Dehmlow H, Ji YH, Gains N, Lengsfeld H, Himber J. Ro 48-8071, a new 2,3-oxidosqualene:lanosterol cyclase inhibitor lowering plasma cholesterol in hamsters, squirrel monkeys, and minipigs: comparison to simvastatin. J Lipid Res. 1997;38:373-390.
14. Mark M, Muller P, Maier R, Eisele B. Effects of a novel 2, 3-oxidosqualene cyclase inhibitor on the regulation of cholesterol biosynthesis in HepG2 cells. J Lipid Res. 1996;37:148-158.
15. Boutaud O, Dolis D, Schuber F. Preferential cyclization of 2,3(S): 22(S),23-dioxidosqualene by mammalian 2,3-oxidosqualene-lanosterol cyclase. Biochem Biophys Res Commun. 1992;188:898-904.
16. Huff MW, Evans AJ, Sawyez CG, Wolfe BM, Nestel PJ. Cholesterol accumulation in J774 macrophages induced by triglyceride-rich lipoproteins: comparison of very low density lipoproteins from subjects with type III, IV, and V hyperlipoproteinemias. Arterioscler Thromb. 1991;11:221-233.
17. Evans AJ, Sawyez CG, Wolfe BM, Connelly PW, Maguire GF, Huff MW. Evidence that cholesterol ester and triglyceride accumulation in J774 macrophages induced by VLDL subfractions occurs by different mechanisms. J Lipid Res. 1993;34:703-717.
18. Whitman SC, Sawyez CG, Miller DB, Wolfe BM, Huff MW. Oxidized type IV hypertriglyceridemic VLDL-remnants cause greater macrophage cholesteryl ester accumulation than oxidized LDL. J Lipid Res. 1998;39:1008-1020.
19. 1 inhibits macrophage cholesteryl ester accumulation induced by native and oxidized VLDL remnants. Arterioscler Thromb Vasc Biol. 2001;21: 2011-2018.
20. Song C, Hiipakka RA, Liao S. Auto-oxidized cholesterol sulfates are antagonistic ligands of liver X receptors: implications for the development and treatment of atherosclerosis. Steroids. 2001;66:473-479.
21. Frolov A, Zielinski S, Crowley J, Dudley-Rucker N, Schaffer J, Ory D. NPC1 and NPC2 regulate cellular cholesterol homeostasis through generation of low density lipoprotein cholesterol-derived oxysterols. J Biol Chem. 2003;278:25517-25525.
22. Grefhorst A, Elzinga BM, Voshol PJ, Plosch T, Kok T, Bloks VW, van der Sluijs FH, Havekes LM, Romijn JA, Verkade HJ, Kuipers F. 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. 2002;277:34182-34190.
23. Spencer TA, Li D, Russel JS, Collins JL, Bledsoe RK, Consler TG, Moore LB, Galardi CM, McKee DD, Moore JT, Watson MA, Parks DJ, Lambert MH, Willson TM. Pharmacophore analysis of the nuclear oxysterol receptor LXRα. J Med Chem. 2001;44:886-897.
24. Schultz JR, Tu H, Luk A, Repa JJ, Medina JC, Li L, Schwendner S, Wang S, Thoolen M, Mangelsdorf DJ, Lustig KD, Shan B. Role of LXRs in control of lipogenesis. Genes Dev. 2000;14:2831-2838.
25. Repa JJ, Liang G, Ou J, Bashmakov Y, Lobaccaro JM, Shimomura I, Shan B, Brown MS, Goldstein JL, Mangelsdorf DJ. Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRα and LXRβ. Genes Dev. 2000;14:2819-2830.
26. Janowski BA, Shan B, Russell DW. The hypocholesterolemic agent LY295427 reverses suppression of sterol regulatory element-binding protein processing mediated by oxysterols. J Biol Chem. 2001;276:45408-45416.
27. Linton MF, Babaev VR, Gleaves LA, Fazio S. A direct role for the macrophage low density lipoprotein receptor in atherosclerotic lesion formation. J Biol Chem. 1999;274:19204-19210.
28. Joseph SB, Laffitte BA, Patel PH, Watson MA, Matsukuma KE, Walczak R, Collins JL, Osborne TF, Tontonoz P. Direct and indirect mechanisms for regulation of fatty acid synthase gene expression by liver X receptors. J Biol Chem. 2002;277:11019-11025.
29. Hannah VC, Ou J, Luong A, Goldstein JL, Brown MS. Unsaturated fatty acids down-regulate SREBP isoforms 1a and 1c by two mechanisms in HEK-293 cells. J Biol Chem. 2001;276:4365-4372.
30. Joseph SB, McKilligin E, Pei L, Watson MA, Collins AR, Laffitte BA, Chen M, Noh G, Goodman J, Hagger GN, Tran J, Tippin TK, Wang X, Lusis AJ, Hsueh WA, Law RE, Collins JL, Willson TM, Tontonoz P. Synthetic LXR ligand inhibits the development of atherosclerosis in mice. Proc Natl Acad Sci U S A. 2002;99:7604-7609.