Oxysterols in biological systems: The gastrointestinal tract, liver, vascular wall and central nervous system

Free Radical Research

Volumn 44, Issue 1, 2010, Pages 47-73

  Garenc, Christophe ^a   Julien, Pierre ^a   Levy, Emile ^b  

^a LAVAL UNIVERSITY   (Canada)

^b UNIVERSITY OF MONTREAL   (Canada)

Author keywords

Alzheimer's disease; Atherosclerosis; Enterocyte; Liver; Nuclear receptors; Oxysterols

Indexed keywords

24 HYDROXYCHOLESTEROL; 26 HYDROXYCHOLESTEROL; 7 OXOCHOLESTEROL; 7BETA HYDROXYCHOLESTEROL; ANTIOXIDANT; BILE ACID; CELL NUCLEUS RECEPTOR; CHOLESTEROL; CHOLESTEROL 5BETA,6BETA OXIDE; LIVER X RECEPTOR; OXYSTEROL; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ATHEROGENESIS; ATHEROSCLEROSIS; ATHEROSCLEROTIC PLAQUE; AUTOOXIDATION; BIOLOGY; BLOOD VESSEL WALL; CARDIOVASCULAR SYSTEM; CENTRAL NERVOUS SYSTEM; CHOLESTEROL METABOLISM; FOAM CELL; GASTROINTESTINAL TRACT; HUMAN; LIPID ABSORPTION; METABOLITE; MOLECULAR BIOLOGY; MOLECULE; NONHUMAN; PATHOPHYSIOLOGY; PHYSIOLOGY; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; BLOOD VESSELS; CENTRAL NERVOUS SYSTEM; ENDOTHELIUM, VASCULAR; GASTROINTESTINAL TRACT; HUMANS; LIVER; MODELS, BIOLOGICAL; STEROLS;

EID: 71649098891     PISSN: 10715762     EISSN: 10292470     Source Type: Journal    
DOI: 10.3109/10715760903321804     Document Type: Review

References (329)

1. Bjorkhem I, Diczfalusy U, Lutjohann D. Removal of cholesterol from extrahepatic sources by oxidative mechanisms. Curr Opin Lipidol 1999;10:161-165.
2. Bjorkhem I. Rediscovery of cerebrosterol. Lipids 2007;42:5-14.
3. Babiker A, Diczfalusy U. Transport of side-chain oxidized oxysterols in the human circulation. Biochim Biophys Acta 1998;1392:333-339.
4. Kandutsch AA, Chen H W. Inhibition of sterol synthesis in cultured mouse cells by cholesterol derivatives oxygenated in the side chain. J Biol Chem 1974;249:6057-6061.
5. Brown MS, Goldstein JL. Suppression of 3-hydroxy-3-meth-ylglutaryl coenzyme A reductase activity and inhibition of growth of human fi broblasts by 7-ketocholesterol. J Biol Chem 1974;249:7306-7314.
6. Danielsson H, Kalles I, Wikvall K. Regulation of hydroxyla-tions in biosynthesis of bile acids. Isolation of a protein from rat liver cytosol stimulating reconstituted cholesterol 7 alpha-hydroxylase activity. J Biol Chem 1984;259:4258-4262.
7. Bjorkhem I, Andersson O, Diczfalusy U, Sevastik B, Xiu RJ, Duan C, Lund E. Atherosclerosis and sterol 27-hydroxylase: evidence for a role of this enzyme in elimination of cholesterol from human macrophages. Proc Natl Acad Sci USA 1994;91:8592-8596.
8. Norlin M, Toll A, Bjorkhem I, Wikvall K. 24-hydroxycholes-terol is a substrate for hepatic cholesterol 7alpha-hydroxylase (CYP7A). J Lipid Res 2000;41:1629-1639.
9. Lutjohann D, Breuer O, Ahlborg G, Nennesmo I, Siden A, Diczfalusy U, Bjorkhem I. Cholesterol homeostasis in human brain: evidence for an age-dependent fl ux of 24S-hydroxy-cholesterol from the brain into the circulation. Proc Natl Acad Sci USA 1996;93:9799-9804.
10. Dietschy JM. Central nervous system: cholesterol turnover, brain development and neurodegeneration. Biol Chem 2009;390:287-293.
11. Lyons MA, Samman S, Gatto L, Brown AJ. Rapid hepatic metabolism of 7-ketocholesterol in vivo: implications for dietary oxysterols. J Lipid Res 1999;40:1846-1857.
12. Schweizer RA, Zurcher M, Balazs Z, Dick B, Odermatt A. Rapid hepatic metabolism of 7-ketocholesterol by 11beta-hydroxysteroid dehydrogenase type 1: species-specifi c differences between the rat, human, and hamster enzyme. J Biol Chem 2004;279:18415-18424.
13. van Reyk DM, Brown AJ, Hult'en LM, Dean RT, Jessup W. Oxysterols in biological systems: sources, metabolism and pathophysiological relevance. Redox Rep 2006;11:255-262.
14. Takahashi K, Takeya M, Sakashita N. Multifunctional roles of macrophages in the development and progression of atherosclerosis in humans and experimental animals. Med Electron Microsc 2002;35:179-203.
15. Schroepfer Jr. GJ. Oxysterols: modulators of cholesterol metabolism and other processes. Physiol Rev 2000;80:361-554.
16. Guardiola F, Dutta PC, Codony GP, Savage GP. Cholesterol and phytosterol oxidation products: Analysis, occurrence, and biological effects. Champaign, Illinois. American Oil Chemists Society; 2002.
17. Bjorkhem I, Diczfalusy U. Oxysterols: friends, foes, or just fellow passengers? Arterioscler Thromb Vasc Biol 2002;22:734-742.
18. Lange Y, Ory DS, Ye J, Lanier MH, Hsu FF, Steck TL. Effectors of rapid homeostatic responses of endoplasmic reticulum cholesterol and 3-hydroxy-3-methylglutaryl-CoA reductase. J Biol Chem 2008;283:1445-1455.
19. Lange Y, Ye J, Strebel F. Movement of 25-hydroxycholesterol from the plasma membrane to the rough endoplasmic reticulum in cultured hepatoma cells. J Lipid Res 1995;36:1092-1097.
20. Bjorkhem I. Are side-chain oxidized oxysterols regulators also in vivo? J Lipid Res 2008; 50(Suppl): S213-218.
21. Brown AJ, Jessup W. Oxysterols and atherosclerosis. Atherosclerosis 1999;142:1-28.
22. Diczfalusy U. Analysis of cholesterol oxidation products in biological samples. J AOAC Int 2004;87:467-473.
23. Bodin K, Andersson U, Rystedt E, Ellis E, Norlin M, Pikuleva I, Eggertsen G, Bjorkhem I, Diczfalusy U. Metabolism of 4 beta-hydroxycholesterol in humans. J Biol Chem 2002;277:31534-31540.
24. Lemaire-Ewing S, Prunet C, Montange T, Vejux A, Berthier A, Bessede G, Corcos L, Gambert P, Neel D, Lizard G Comparison of the cytotoxic, pro-oxidant and pro-infl ammatory characteristics of different oxysterols. Cell Biol Toxicol 2005;21:97-114.
25. Vejux A, Lizard G. Cytotoxic effects of oxysterols associated with human diseases: induction of cell death (apoptosis and/ or oncosis), oxidative and infl ammatory activities, and phos-pholipidosis. Mol Aspects Med 2009; 30:153-170.
26. Vejux A, Malvitte L, Lizard G. Side effects of oxysterols: cyto-toxicity, oxidation, infl ammation, and phospholipidosis. Braz J Med Biol Res 2008;41:545-556.
27. Lordan S, O'Callaghan YC, O'Brien NM. Death-signaling pathways in human myeloid cells by oxLDL and its cytotoxic components 7beta-hydroxycholesterol and cholesterol-5beta, 6beta-epoxide. J Biochem Molec Toxicol 2007;21:362-372.
28. Massey JB. Membrane and protein interactions of oxysterols. Curr Opin Lipidol 2006;17:296-301.
29. Torocsik D, Szanto A, Nagy L. Oxysterol signaling links cholesterol metabolism and infl ammation via the liver X receptor in macrophages. Mol Aspects Med 2009; 30:134-152.
30. Vejux A, Guyot S, Montange T, Riedinger JM, Kahn E, Lizard G. Phospholipidosis and down-regulation of the PI3-K/PDK-1/ Akt signalling pathway are vitamin E inhibitable events associated with 7-ketocholesterol-induced apoptosis. J Nutr Bio-chem 2009;20:45-61.
31. Biasi F, Leonarduzzi G, Vizio B, Zanetti D, Sevanian A, Sottero B, Verde V, Zingaro B, Chiarpotto E, Poli G. Oxysterol mixtures prevent proapoptotic effects of 7-ketocholesterol in macrophages: implications for proatherogenic gene modulation. Faseb J 2004;18:693-695.
32. Larsson DA, Baird S, Nyhalah JD, Yuan XM, Li W Oxysterol mixtures, in atheroma-relevant proportions, display synergistic and proapoptotic effects. Free Radic Biol Med 2006;41:902-910.
33. Colles SM, Maxson JM, Carlson SG, Chisolm GM. Oxidized LDL-induced injury and apoptosis in atherosclerosis. Potential roles for oxysterols. Trends Cardiovasc Med 2001;11:131-138.
34. Kockx MM, Herman AG. Apoptosis in atherosclerosis: ben-efi cial or detrimental? Cardiovasc Res 2000;45:736-746.
35. Kockx MM. Apoptosis in the atherosclerotic plaque: quantitative and qualitative aspects. Arterioscler Thromb Vasc Biol 1998;18:1519-1522.
36. Anderson N, Borlak J. Drug-induced phospholipidosis. FEBS Lett 2006;580:5533-5540.
37. Piccotti JR, LaGattuta MS, Knight SA, Gonzales AJ, Bleavins MR. Induction of apoptosis by cationic amphiphilic drugs amiodarone and imipramine. Drug Chem Toxicol 2005;28:117-133.
38. 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 defi nes a new hormone response pathway. J Biol Chem 1997;272:3137-3140.
39. Janowski BA, Willy PJ, Devi TR, Falck JR, Mangelsdorf DJ. An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature 1996;383:728-731.
40. Zelcer N, Tontonoz P. Liver X receptors as integrators of metabolic and infl ammatory signaling. J Clin Invest 2006;116:607-614.
41. Cai TQ, Wong B, Mundt SS, Thieringer R, Wright SD, Her-manowski-Vosatka A. Induction of 11beta-hydroxysteroid dehydrogenase type 1 but not-2 in human aortic smooth muscle cells by infl ammatory stimuli. J Steroid Biochem Mol Biol 2001;77:117-122.
42. Thieringer R, Le Grand CB, Carbin L, Cai TQ, Wong B, Wright SD, Hermanowski-Vosatka A. 11 Beta-hydroxysteroid dehydrogenase type 1 is induced in human monocytes upon differentiation to macrophages. J Immunol 2001;167:30-35.
43. Schwarz M, Lund EG, Russell DW. Two 7 alpha-hydroxylase enzymes in bile acid biosynthesis. Curr Opin Lipidol 1998;9:113-118.
44. Chiang JY. Regulation of bile acid synthesis: pathways, nuclear receptors, and mechanisms. J Hepatol 2004;40:539-551.
45. Lund EG, Guileyardo JM, Russell DW. cDNA cloning of cholesterol 24-hydroxylase, a mediator of cholesterol homeostasis in the brain. Proc Natl Acad Sci USA 1999;96:7238-7243.
46. Lutjohann D, Papassotiropoulos A, Bjorkhem I, Locatelli S, Bagli M, Oehring RD, Schlegel U, Jessen F, Rao ML, von Bergmann K, Heun R. Plasma 24S-hydroxycholesterol (cer-ebrosterol) is increased in Alzheimer and vascular demented patients. J Lipid Res 2000;41:195-198.
47. Meaney S, Hassan M, Sakinis A, Lutjohann D, von Bergmann K, Wennmalm A, Diczfalusy U, Bjorkhem I. Evidence that the major oxysterols in human circulation originate from distinct pools of cholesterol: a stable isotope study. J Lipid Res 2001;42:70-78.
48. Lund EG, Kerr TA, Sakai J, Li WP, Russell DW. cDNA cloning of mouse and human cholesterol 25-hydroxylases, polytopic membrane proteins that synthesize a potent oxysterol regulator of lipid metabolism. J Biol Chem 1998;273:34316-34327.
49. Faust JR, Luskey KL, Chin DJ, Goldstein JL, Brown MS. Regulation of synthesis and degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase by low density lipopro-tein and 25-hydroxycholesterol in UT-1 cells. Proc Natl Acad Sci USA 1982;79:5205-5209.
50. Radhakrishnan A, Ikeda Y, Kwon HJ, Brown MS, Goldstein JL. Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: oxysterols block transport by binding to Insig. Proc Natl Acad Sci USA 2007;104:6511-6518.
51. Sun LP, Seemann J, Goldstein JL, Brown MS. Sterol-regu-lated transport of SREBPs from endoplasmic reticulum to Golgi: Insig renders sorting signal in Scap inaccessible to COPII proteins. Proc Natl Acad Sci USA 2007;104: 6519-6526.
52. Babiker A, Andersson O, Lund E, Xiu RJ, Deeb S, Reshef A, Leitersdorf E, Diczfalusy U, Bjorkhem I. Elimination of cholesterol in macrophages and endothelial cells by the sterol 27-hydroxylase mechanism. Comparison with high density lipoprotein-mediated reverse cholesterol transport. J Biol Chem 1997;272:26253-26261.
53. Andersson S, Davis DL, Dahlback H, Jornvall H, Russell DW. Cloning, structure, and expression of the mitochondrial cyto-chrome P-450 sterol 26-hydroxylase, a bile acid biosynthetic enzyme. J Biol Chem 1989;264:8222-8229.
54. Crisby M, Nilsson J, Kostulas V, Bjorkhem I, Diczfalusy I. Localization of sterol 27-hydroxylase immuno-reactivity in human atherosclerotic plaques. Biochim Biophys Acta 1997;1344:278-285.
55. Shanahan CM, Carpenter KL, Cary NR. A potential role for sterol 27-hydroxylase in atherogenesis. Atherosclerosis 2001;154:269-276.
56. Lund E, Andersson O, Zhang J, Babiker A, Ahlborg G, Dic-zfalusy U, Einarsson K, Sjovall J, Bjorkhem I. Importance of a novel oxidative mechanism for elimination of intracellular cholesterol in humans. Arterioscler Thromb Vasc Biol 1996;16:208-212.
57. Duane WC, Javitt NB. 27-hydroxycholesterol: production rates in normal human subjects. J Lipid Res 1999;40: 1194-1199.
58. Russell DW. Oxysterol biosynthetic enzymes. Biochim Bio-phys Acta 2000;1529:126-135.
59. Reiss AB, Martin KO, Javitt NB, Martin DW, Grossi EA, Galloway AC. Sterol 27-hydroxylase: high levels of activity in vascular endothelium. J Lipid Res 1994;35:1026-1030.
60. Hirayama T, Mizokami Y, Honda A, Homma Y, Ikegami T, Saito Y, Miyazaki T, Matsuzaki Y. Serum concentration of 27-hydroxycholesterol predicts the effects of high-cholesterol diet on plasma LDL cholesterol level. Hepatol Res 2009;39:149-156.
61. Rowe AH, Argmann CA, Edwards JY, Sawyez CG, Morand OH, Hegele RA, Huff MW. Enhanced synthesis of the oxys-terol 24(S),25-epoxycholesterol in macrophages by inhibitors of 2,3-oxidosqualene:lanosterol cyclase: a novel mechanism for the attenuation of foam cell formation. Circulat Res 2003;93:717-725.
62. Spencer TA Gayen AK, Phirwa S, Nelson JA, Taylor FR, Kandutsch AA, Erickson SK. 24(S),25-Epoxycholesterol. Evidence consistent with a role in the regulation of hepatic cholesterogenesis. J Biol Chem 1985;260:13391-13394.
63. Wong J, Quinn CM, Brown AJ. Statins inhibit synthesis of an oxysterol ligand for the liver x receptor in human macro-phages with consequences for cholesterol fl ux. Arterioscler Thromb Vasc Biol 2004;24:2365-2371.
64. Janowski BA, Grogan MJ, Jones SA, Wisely GB, Kliewer SA, Corey EJ, Mangelsdorf DJ. Structural requirements of ligands for the oxysterol liver X receptors LXRalpha and LXRbeta. Proc Natl Acad Sci USA1999;96:266-271.
65. Fu X, Menke JG, Chen Y, Zhou G, MacNaul KL, Wright GD, 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.
66. Wong J, Quinn CM, Brown AJ. Synthesis of the oxysterol, 24(S), 25-epoxycholesterol, parallels cholesterol production and may protect against cellular accumulation of newly-synthesized cholesterol. Lipids Health Dis 2007;6:10.
67. Zhang Z, Li D, Blanchard DE, Lear SR, Erickson SK, Spencer TA. Key regulatory oxysterols in liver: analysis as delta4-3-ketone derivatives by HPLC and response to physiological perturbations. J Lipid Res 2001;42:649-658.
68. Hamosh M. Lingual and gastric lipase: their role in fat digestion. Boca Raton, Florida: CRC Press; 1990.
69. Levy E, Goldstein R, Freier S,Shafrir E. Characterization of gastric lipolytic activity. Biochim Biophys Acta 1981;664: 316-326.
70. Verger R. Pancreatic lipases. In: Borgström B, Brockman HL, editors. Lipases. New York: Elsevier; 1984. p 84-150.
71. Patton JS. Gastrointestinal lipid digestion. In: Johnson LR, editor. Physiology of the gastrointestinal tract. New York: Raven Press; 1981. p 1123.
72. Carey MC, Small DM, Bliss CM. Lipid digestion and absorption. Annu Rev Physiol 1983;45:651-677.
73. Nalbone G, Lairon D, Lafont H, Domingo N, Hauton J, Sarda L. Behavior of biliary phospholipids in intestinal lumen during fat digestion in rat. Lipids 1974;9:765-770.
74. Mansbach 2nd CM, Cohen RS, Leff PB. Isolation and properties of the mixed lipid micelles present in intestinal content during fat digestion in man. J Clin Invest 1975;56:781-791.
75. Patton JS, Carey MC. Watching fat digestion. Science 1979;204:145-148.
76. Hernell O, Staggers JE, Carey MC. Physical-chemical behavior of dietary and biliary lipids during intestinal digestion and absorption. 2. Phase analysis and aggregation states of luminal lipids during duodenal fat digestion in healthy adult human beings. Biochemistry 1990;29:2041-2056. (Pubitemid 20085429)
77. Levy E, Spahis S, Sinnett D, Peretti N, Maupas-Schwalm F, Delvin E, Lambert M, Lavoie MA. Intestinal cholesterol transport proteins: an update and beyond. Curr Opin Lipidol 2007;18:310-318.
78. Levy E, Stan S, Garofalo C, Delvin EE, Seidman EG, Menard D. Immunolocalization, ontogeny, and regulation of microsomal triglyceride transfer protein in human fetal intestine. Am J Physiol Gastrointest Liver Physiol 2001;280:G563-G571.
79. Wetterau JR, Aggerbeck LP, Bouma ME, Eisenberg C, Munck A, Hermier M, Schmitz J, Gay G, Rader DJ, Gregg RE. Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia. Science 1992;258:999-1001.
80. Repa JJ, Mangelsdorf DJ. The role of orphan nuclear receptors in the regulation of cholesterol homeostasis. Annu Rev Cell Dev Biol 2000;16:459-481.
81. Edwards PA, Kennedy MA, Mak PA. LXRs; oxysterol-acti-vated nuclear receptors that regulate genes controlling lipid homeostasis. Vasc Pharmacol 2002;38:249-256.
82. Lund EG, Menke JG, Sparrow CP. Liver X receptor agonists as potential therapeutic agents for dyslipidemia and atherosclerosis. Arterioscler Thromb Vasc Biol 2003;23: 1169-1177.
83. Repa JJ, Berge KE, Pomajzl C, Richardson JA, Hobbs H, Mangelsdorf DJ. Regulation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 by the liver X receptors alpha and beta. J Biol Chem 2002;277:18793-18800.
84. Yu L, York J, von Bergmann K, Lutjohann D, Cohen JC, Hobbs HH. Stimulation of cholesterol excretion by the liver X receptor agonist requires ATP-binding cassette transporters G5 and G8. J Biol Chem 2003;278:15565-15570.
85. Quinet EM, Savio DA, Halpern AR, Chen L, Miller CP, Nambi P. Gene-selective modulation by a synthetic oxysterol ligand of the liver X receptor. J Lipid Res 2004;45: 1929-1942.
86. Ma Y, Xu L, Rodriguez-Agudo D, Li X, Heuman DM, Hylemon PB, Pandak WM, Ren S. 25-Hydroxycholesterol-3-Sulfate (25HC3S) regulates macrophage lipid metabolism via the LXR/SREBP-1 signaling pathway. Am J Physiol 2008;295:E1369-E1379.
87. Terasaka N, Yu S, Yvan-Charvet L, Wang N, Mzhavia N, Lan-glois R, Pagler T, Li R, Welch CL, Goldberg IJ, Tall AR. ABCG1 and HDL protect against endothelial dysfunction in mice fed a high-cholesterol diet. J Clin Invest 2008;118:3701-3713.
88. Costet P, Luo Y, Wang N, Tall AR. Sterol-dependent transac-tivation of the ABC1 promoter by the liver X receptor/retinoid X receptor. J Biol Chem 2000;275:28240-28245.
89. Kennedy MA, Venkateswaran A, Tarr PT, Xenarios I, Kudoh J, Shimizu N, Edwards PA. Characterization of the human ABCG1 gene: liver X receptor activates an internal promoter that produces a novel transcript encoding an alternative form of the protein. J Biol Chem 2001;276:39438-39447. (Pubitemid 37371322)
90. Sparrow CP, Baffi c 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 ABCA1 mRNA and stimulating cholesterol effl ux. J Biol Chem 2002;277:10021-10027.
91. Venkateswaran A, Repa JJ, Lobaccaro JM, Bronson A, Man-gelsdorf DJ, Edwards PA. Human white/murine ABC8 mRNA levels are highly induced in lipid-loaded macrophages. A tran-scriptional role for specifi c oxysterols. J Biol Chem 2000;275:14700-14707.
92. Wang N, Ranalletta M, Matsuura F, Peng F, Tall AR. LXR-induced redistribution of ABCG1 to plasma membrane in macrophages enhances cholesterol mass effl ux to HDL. Arte-rioscler Thromb Vasc Biol 2006;26:1310-1316.
93. 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. Intestinal ABCA1 directly contributes to HDL biogenesis in vivo. J Clin Invest 2006;116:1052-1062.
94. Duval C, Touche V, Tailleux A, Fruchart JC, Fievet C, Clavey V, Staels B, Lestavel S. Niemann-Pick C1 like 1 gene expression is down-regulated by LXR activators in the intestine. Biochem Biophys Res Comm 2006;340:1259-1263.
95. Ravid Z, Bendayan M, Delvin E, Sane AT, Elchebly M, Lafond J, Lambert M, Mailhot G, Levy E. Modulation of intestinal cholesterol absorption by high glucose levels: impact on cholesterol transporters, regulatory enzymes, and transcription factors. Am J Physiol Gastrointest Liver Physiol 2008;295:G873-G885.
96. Marcil V, Delvin E, Sane AT, Tremblay A, Levy E. Oxidative stress infl uences cholesterol effl ux in THP-1 macrophages: role of ATP-binding cassette A1 and nuclear factors. Cardio-vasc Res 2006;72:473-482.
97. Peretti N, Delvin E, Sinnett D, Marcil V, Garofalo C, Levy E. Asymmetrical regulation of scavenger receptor class B type I by apical and basolateral stimuli using Caco-2 cells. J Cell Biochem 2007;100:421-433.
98. Sane AT, Sinnett D, Delvin E, Bendayan M, Marcil V, Menard D, Beaulieu JF, Levy E. Localization and role of NPC1L1 in cholesterol absorption in human intestine. J Lipid Res 2006;47:2112-2120.
99. Hofmann AF. The continuing importance of bile acids in liver and intestinal disease. Arch Intern Med 1999;159:2647-2658.
100. Houten SM, Watanabe M, Auwerx J. Endocrine functions of bile acids. EMBO J 2006;25:1419-1425.
101. Chawla A, Saez E,Evans RM. Don't know much bile-ology. Cell 2000;103:1-4.
102. Russell DW. The enzymes, regulation, and genetics of bile acid synthesis. Annu Rev Biochem 2003;72:137-174.
103. Redinger RN. Nuclear receptors in cholesterol catabolism: molecular biology of the enterohepatic circulation of bile salts and its role in cholesterol homeostasis. J Lab Clin Med 2003;142:7-20.
104. Angelin B, Eriksson M, Rudling M. Bile acids and lipopro-tein metabolism: a renaissance for bile acids in the post-statin era? Curr Opin Lipidol 1999;10:269-274.
105. Hoeg JM. Pharmacologic and surgical treatment of dyslipi-demic children and adolescents. Ann NY Acad Sci 1991;623:275-284.
106. Vlahcevic ZR, Heuman DM, Hylemon PB. Regulation of bile acid synthesis. Hepatology 1991;13:590-600.
107. Turley SD, Dietschy JM. Cholesterol metabolism and excretion. In: Arias JM, Popper H, Schachter I, Shafritz DA, editors. The liver: Biology and pathobiology. New York: Raven Press; 1982. p 467-492.
108. Spady DK, Cuthbert JA. Regulation of hepatic sterol metabolism in the rat. Parallel regulation of activity and mRNA for 7 alpha-hydroxylase but not 3-hydroxy-3-methylglutaryl-coenzyme A reductase or low density lipoprotein receptor. J Biol Chem 1992;267:5584-5591.
109. Shefer S, Nguyen LB, Salen G, Ness GC, Chowdhary IR, Lerner S, Batta AK, Tint GS. Differing effects of cholesterol and taurocholate on steady state hepatic HMG-CoA reduct-ase and cholesterol 7 alpha-hydroxylase activities and mRNA levels in the rat. J Lipid Res 1992;33:1193-1200.
110. Haigh WG, Lee SP. Identifi cation of oxysterols in human bile and pigment gallstones. Gastroenterology 2001;121:118-123.
111. Seo DW, Choi HS, Lee SP, Kuver R. Oxysterols from human bile induce apoptosis of canine gallbladder epithelial cells in monolayer culture. Am J Physiol Gastrointest Liver Physiol 2004;287:G1247-G1256.
112. Javitt NB. Bile acid synthesis from cholesterol: regulatory and auxiliary pathways. FASEB J 1994;8:1308-1311.
113. Diczfalusy U, Lund E, Lutjohann D, Bjorkhem I. Novel pathways for elimination of cholesterol by extrahepatic formation of side-chain oxidized oxysterols. Scand J Clin Lab Invest Suppl 1996;226:9-17.
114. Dietschy JM, Turley SD, Spady DK. Role of liver in the maintenance of cholesterol and low density lipoprotein homeostasis in different animal species, including humans. J Lipid Res 1993;34:1637-1659.
115. Shneider BL. Intestinal bile acid transport: biology, physiology, and pathophysiology. J Pediat Gastroenterol Nutr 2001;32:407-417.
116. Walters HC, Craddock AL, Fusegawa H, Willingham MC, Dawson PA. Expression, transport properties, and chromosomal location of organic anion transporter subtype 3. Am J Physiol Gastrointest Liver Physiol 2000;279: G1188-G1200.
117. Abe T, Kakyo M, Sakagami H, Tokui T, Nishio T, Tanemoto M, Nomura H, Hebert SC, Matsuno S, Kondo H, Yawo H. Molecular characterization and tissue distribution of a new organic anion transporter subtype (oatp3) that transports thyroid hormones and taurocholate and comparison with oatp2. J Biol Chem 1998;273:22395-22401.
118. Dawson PA, Hubbert M, Haywood J, Craddock AL, Zerangue N, Christian WV, Ballatori N. The heteromeric organic solute transporter alpha-beta, Ostalpha-Ostbeta, is an ileal basolateral bile acid transporter. J Biol Chem 2005;280: 6960-6968.
119. Okuwaki M, Takada T, Iwayanagi Y, Koh S, Kariya Y, Fujii H, Suzuki H. LXR alpha transactivates mouse organic solute transporter alpha and beta via IR-1 elements shared with FXR. Pharm Res 2007;24:390-398.
120. Vine DF, Croft KD, Beilin LJ,Mamo JC. Effect of dietary cholesterol oxidation products on the plasma clearance of chylomicrons in the rat. Lipids 2002;37:455-462.
121. Vine DF, Mamo CL, Beilin LJ, Mori TA, Croft KD. Dietary oxysterols are incorporated in plasma triglyceride-rich lipo-proteins, increase their susceptibility to oxidation and increase aortic cholesterol concentration of rabbits. J Lipid Res 1998;39:1995-2004.
122. Griffi ths WJ, Hornshaw M, Woffendin G, Baker SF, Lockhart A, Heidelberger S, Gustafsson M, Sjovall J, Wang Y. Discovering oxysterols in plasma: a window on the metabolome. J Pro-teome Res 2008;7:3602-3612.
123. Patel NT, Thompson EB. Human oxysterol-binding protein. I. Identifi cation and characterization in liver. J Clin Endocrinol Metab 1990;71:1637-1645.
124. Mortimer BC, Tso P, Phan CT, Beveridge DJ, Wen J, Redgrave TG. Features of cholesterol structure that regulate the clearance of chylomicron-like lipid emulsions. J Lipid Res 1995;36:2038-2053.
125. Hodis HN, Crawford DW, Sevanian A. Cholesterol feeding increases plasma and aortic tissue cholesterol oxide levels in parallel: further evidence for the role of cholesterol oxidation in atherosclerosis. Atherosclerosis 1991;89:117-126.
126. Hodis HN, Chauhan A, Hashimoto S, Crawford DW, Sevanian A. Probucol reduces plasma and aortic wall oxysterol levels in cholesterol fed rabbits independently of its plasma cholesterol lowering effect. Atherosclerosis 1992;96:125-134.
127. Kozarsky KF, Donahee MH, Rigotti A, Iqbal SN, Edelman ER, Krieger M. Overexpression of the HDL receptor SR-BI alters plasma HDL and bile cholesterol levels. Nature 1997;387:414-417.
128. Fluiter K, Sattler W, De Beer MC, Connell PB, van der Westhuyzen DR, van Berkel TJ. Scavenger receptor BI mediates the selective uptake of oxidized cholesterol esters by rat liver. J Biol Chem 1999;274:8893-8899.
129. Trauner M, Boyer JL. Bile salt transporters: molecular characterization, function, and regulation. Physiol Rev 2003;83:633-671.
130. von Dippe P, Amoui M, Stellwagen RH, Levy D. The functional expression of sodium-dependent bile acid transport in Madin-Darby canine kidney cells transfected with the cDNA for microsomal epoxide hydrolase. J Biol Chem 1996;271:18176-18180.
131. Kullak-Ublick GA, Stieger B, Meier PJ. Enterohepatic bile salt transporters in normal physiology and liver disease. Gas-troenterology 2004;126:322-342. (Pubitemid 38040747)
132. Meier PJ. Molecular mechanisms of hepatic bile salt transport from sinusoidal blood into bile. Am J Physiol 1995;269:G801-G812.
133. Hagenbuch B, Meier PJ. Organic anion transporting polypeptides of the OATP/ SLC21 family: phylogenetic clas-sifi cation as OATP/ SLCO superfamily, new nomenclature and molecular/functional properties. Pfl ugers Arch 2004;447:653-665.
134. Suchy FJ, Ananthanarayanan M. Bile salt excretory pump: biology and pathobiology. J Pediat Gastroenterol Nutr 2006;43(Suppl 1):S10-S16.
135. St-Pierre MV, Kullak-Ublick GA, Hagenbuch B, Meier PJ. Transport of bile acids in hepatic and non-hepatic tissues. J Exp Biol 2001;204:1673-1686.
136. Deng R, Yang D, Yang J, Yan B. Oxysterol 22(R)-hydroxyc-holesterol induces the expression of the bile salt export pump through nuclear receptor farsenoid X receptor but not liver X receptor. J Pharmacol Exp Therapeut 2006;317:317-325.
137. Dzeletovic S, Breuer O, Lund E, Diczfalusy U. Determination of cholesterol oxidation products in human plasma by isotope dilution-mass spectrometry. Anal Biochem 1995; 225:73-80.
138. Lin CY, Morel DW. Esterifi cation of oxysterols in human serum: effects on distribution and cellular uptake. J Lipid Res 1996;37:168-178.
139. Bjorkhem I, Reihner E, Angelin B, Ewerth S, Akerlund JE, Einarsson K. On the possible use of the serum level of 7 alpha-hydroxycholesterol as a marker for increased activity of the cholesterol 7 alpha-hydroxylase in humans. J Lipid Res 1987;28:889-894.
140. Prunet C, Montange T, Vejux A, Laubriet A, Rohmer JF, Riedinger JM, Athias A, Lemaire-Ewing S, Neel D, Petit JM, Steinmetz E, Brenot R, Gambert P, Lizard G. Multiplexed fl ow cytometric analyses of pro-and anti-infl ammatory cytokines in the culture media of oxysterol-treated human monocytic cells and in the sera of atherosclerotic patients. Cytometry A 2006;69:359-373.
141. Zieden B, Kaminskas A, Kristenson M, Kucinskiene Z, Vessby B, Olsson AG, Diczfalusy U. Increased plasma 7 beta-hydroxycholesterol concentrations in a population with a high risk for cardiovascular disease. Arterioscler Thromb Vasc Biol 1999;19:967-971.
142. Javitt NB. Oxysterols: novel biologic roles for the 21st century. Steroids 2007;73:149-157.
143. Kellner-Weibel G, Geng YJ, Rothblat GH. Cytotoxic cholesterol is generated by the hydrolysis of cytoplasmic cholesteryl ester and transported to the plasma membrane. Atherosclerosis 1999;146:309-319.
144. Vaya J, Aviram M, Mahmood S, Hayek T, Grenadir E, Hoffman A, Milo S. Selective distribution of oxysterols in atherosclerotic lesions and human plasma lipoproteins. Free Radic Res 2001;34:485-497.
145. Hultén LM, Lindmark H, Diczfalusy U, Björkhem I, Ottosson M, Liu Y, Bondjers G, Wiklund O. Oxysterols present in atherosclerotic tissue decrease the expression of lipoprotein lipase messenger RNA in human monocyte-de-rived macrophages. J Clin Invest 1996;97:461-468.
146. Maor I, Kaplan M, Hayek T, Vaya J, Hoffman A, Aviram M. Oxidized monocyte-derived macrophages in aortic atherosclerotic lesion from apolipoprotein E-defi cient mice and from human carotid artery contain lipid peroxides and oxysterols. Biochem Biophys Res Comm 2000;269: 775-780.
147. Van Cruchten S, Van Den Broeck W. Morphological and biochemical aspects of apoptosis, oncosis and necrosis. Anat Histol Embryol 2002;31:214-223.
148. Steinbrecher UP, Gomez-Munoz A, Duronio V. Acid sphin-gomyelinase in macrophage apoptosis. Curr Opin Lipidol 2004;15:531-537.
149. Ryan L, O'Callaghan YC, O'Brien NM. Generation of an oxidative stress precedes caspase activation during 7beta-hydroxycholesterol-induced apoptosis in U937 cells. J Bio-chem Mol Toxicol 2004;18:50-59.
150. Lizard G, Monier S, Cordelet C, Gesquiere L, Deckert V, Gueldry S, Lagrost L, Gambert P. Characterization and comparison of the mode of cell death, apoptosis versus necrosis, induced by 7beta-hydroxycholesterol and 7-ketoc-holesterol in the cells of the vascular wall. Arterioscler Thromb Vasc Biol 1999;19:1190-1200.
151. Panini SR Sinensky MS. Mechanisms of oxysterol-induced apoptosis. Curr Opin Lipidol 2001;12:529-533.
152. Prunet C, Lemaire-Ewing S, Menetrier F, Neel D, Lizard G. Activation of caspase-3-dependent and-independent pathways during 7-ketocholesterol-and 7beta-hydroxycholester-ol-induced cell death: a morphological and biochemical study. J Biochem Mol Toxicol 2005;19:311-326.
153. Lizard G, Miguet C, Bessede G, Monier S, Gueldry S, Neel D, Gambert P. Impairment with various antioxidants of the loss of mitochondrial transmembrane potential and of the cytosolic release of cytochrome c occuring during 7-ketocholesterol-induced apoptosis. Free Radic Biol Med 2000;28:743-753.
154. Miguet-Alfonsi C, Prunet C, Monier S, Bessede G, Lemaire-Ewing S, Berthier A, Menetrier F, Neel D, Gambert P, Lizard G. Analysis of oxidative processes and of myelin fi gures formation before and after the loss of mitochondrial transmembrane potential during 7beta-hydroxycholesterol and 7-ketocholes-terol-induced apoptosis: comparison with various pro-apop-totic chemicals. Biochem Pharmacol 2002;64:527-541.
155. Lizard G, Gueldry S, Sordet O, Monier S, Athias A, Miguet C, Bessede G, Lemaire S, Solary E, Gambert P. Glutathione is implied in the control of 7-ketocholesterol-induced apopto-sis, which is associated with radical oxygen species production. Faseb J 1998;12:1651-1663.
156. Miguet C, Monier S, Bettaieb A, Athias A, Bessede G, Lau-briet A, Lemaire S, Neel D, Gambert P, Lizard G. Ceramide generation occurring during 7beta-hydroxycholesterol-and 7-ketocholesterol-induced apoptosis is caspase independent and is not required to trigger cell death. Cell Death Differ 2001;8:83-99.
157. Vejux A, Lizard G, Tourneur Y, Riedinger JM, Frouin F, Kahn E. Effects of caspase inhibitors (z-VAD-fmk, z-VDVAD-fmk) on Nile Red fl uorescence pattern in 7-ketocholesterol-treated cells: investigation by fl ow cytometry and spectral imaging microscopy. Cytometry A 2007;71:550-562.
158. Vejux A, Kahn E, Dumas D, Bessede G, Menetrier F, Athias A, Riedinger JM, Frouin F, Stoltz JF, Ogier-Denis E, Todd-Pokropek A, Lizard G. 7-Ketocholesterol favors lipid accumulation and colocalizes with Nile Red positive cytoplasmic structures formed during 7-ketocholesterol-induced apopto-sis: analysis by fl ow cytometry, FRET biphoton spectral imaging microscopy, and subcellular fractionation. Cytom-etry A 2005;64:87-100.
159. Rho MC, Kim YK, Chang JS, Lee HS, Baek JA, Chung MY, Lee HC, Lee HW, Rhim BY, Reidy MA, Kim K. 7-Ketoc-holesterol predisposes human aorta smooth muscle cells to Fas-mediated death. J Mol Cell Cardiol 2005;39:823-832.
160. Seye CI, Knaapen MW, Daret D, Desgranges C, Herman AG, Kockx MM, Bult H. 7-Ketocholesterol induces reversible cytochrome c release in smooth muscle cells
161. Pedruzzi E, Guichard C, Ollivier V, Driss F, Fay M, Prunet C, Marie JC, Pouzet C, Samadi M, Elbim C, O'Dowd Y, Bens M, Vandewalle A, Gougerot-Pocidalo AM, Lizard G, Ogier-Denis E. NAD(P)H oxidase Nox-4 mediates 7-ketocholes-terol- induced endoplasmic reticulum stress and apoptosis in human aortic smooth muscle cells. Mol Cell Biol 2004;24:10703-10717.
162. O'Callaghan YC, Woods JA, O'Brien NM. Comparative study of the cytotoxicity and apoptosis-inducing potential of commonly occurring oxysterols. Cell Biol Toxicol 2001;17:127-137.
163. Ryan E, Chopra J, McCarthy F, Maguire AR, O'Brien NM. Qualitative and quantitative comparison of the cytotoxic and apoptotic potential of phytosterol oxidation products with their corresponding cholesterol oxidation products. Br J Nutr 2005;94:443-451.
164. Li W, Dalen H, Eaton JW, Yuan XM. Apoptotic death of infl ammatory cells in human atheroma. Arterioscler Thromb Vasc Biol 2001;21:1124-1130.
165. Li W, Hellsten A, Xu LH, Zhuang DM, Jansson K, Brunk UT, Yuan XM. Foam cell death induced by 7beta-hydroxy-cholesterol is mediated by labile iron-driven oxidative injury: mechanisms underlying induction of ferritin in human atheroma. Free Radic Biol Med 2005;39:864-875.
166. Pang JH, Jiang MJ, Chen YL, Wang FW, Wang DL, Chu SH, Chau LY. Increased ferritin gene expression in atherosclerotic lesions. J Clin Invest 1996;97:2204-2212.
167. You SA. Wang Q. Ferritin in atherosclerosis. Clin Chim Acta 2005;357:1-16.
168. O'Sullivan A J, O'Callaghan Y C, O'Brien N M. Differential effects of mixtures of cholesterol oxidation products on bovine aortic endothelial cells and human monocytic U937 cells. Int J Toxicol 2005;24:173-179.
169. Aupeix K, Weltin D, Mejia JE, Christ M, Marchal J, Freys-sinet JM, Bischoff P. Oxysterol-induced apoptosis in human monocytic cell lines. Immunobiology 1995;194:415-428.
170. Ryan L, O'Callaghan YC, O'Brien NM. Comparison of the apoptotic processes induced by the oxysterols 7beta-hydrox-ycholesterol and cholesterol-5beta, 6beta-epoxide. Cell Biol Toxicol 2004;20:313-323.
171. Rigamonti E, Helin L, Lestavel S, Mutka AL, Lepore M, Fontaine C, Bouhlel MA, Bultel S, Fruchart JC, Ikonen E, Clavey V, Staels B, Chinetti-Gbaguidi G. Liver X receptor activation controls intracellular cholesterol traffi cking and esterifi cation in human macrophages. Circ Res 2005;97:682-689.
172. Lukiw WJ. Cholesterol and 24S-hydroxycholesterol traffi-cking in Alzheimer's disease. Expert Rev Neurother 2006; 6:683-693.
173. Leoni V. Oxysterols as markers of neurological disease-a review. Scand J Clin Lab Invest 2009;69:22-25.
174. Heverin M, Bogdanovic N, Lütjohann DL, Bayer T, Pikuleva I, Bretillon L, Diczfalusy U, Winblad B, Björkhem I. Changes in the levels of cerebral and extracerebral sterols in the brain of patients with Alzheimer's disease. J Lipid Res 2004;45:186-193.
175. Leoni V, Mariotti C, Tabrizi SJ, Valenza M, Wild EJ, Henley SM, Hobbs NZ, Mandelli ML, Grisoli M, Bjorkhem I, Cattaneo E, Di Donato S. Plasma 24S-hydroxycholesterol and caudate MRI in pre-manifest and early Huntington's disease. Brain 2008;131:2851-2859.
176. Bjorkhem I, Cedazo-Minguez A, Leoni V, Meaney S. Oxyster-ols and neurodegenerative diseases. Mol Aspects Med 2009; 30:171-179.
177. Trousson A, Bernard S, Petit PX, Liere P, Pianos A, El Hadri K, Lobaccaro JM, Said Ghandour M, Raymondjean M, Schumacher M, Massaad C. 25-hydroxycholesterol provokes oli-godendrocyte cell line apoptosis and stimulates the secreted phospholipase A2 type IIA via LXR beta and PXR. J Neu-rochem 2009; 109:945-958.
178. Teunissen CE, Dijkstra CD, Polman CH, Hoogervorst EL, von Bergmann K, Lutjohann D. Decreased levels of the brain specifi c 24S-hydroxycholesterol and cholesterol precursors in serum of multiple sclerosis patients. Neurosci Lett 2003;347:159-162.
179. Leoni V, Masterman T, Diczfalusy U, De Luca G, Hillert J, Bjorkhem I. Changes in human plasma levels of the brain specifi c oxysterol 24S-hydroxycholesterol during progression of multiple sclerosis. Neurosci Lett 2002;331:163-166.
180. Weiner MF, Vega GL, Diaz-Arrastia R, Moore C, Madden C, Hudak A, Lutjohann D. Plasma 24S-hydroxycholesterol and other oxysterols in acute closed head injury. Brain Inj 2008;22:611-615.
181. Cartagena CM, Ahmed F, Burns MP, Pajoohesh-Ganji A, Pak DT, Faden AI, Rebeck GW. Cortical injury increases cholesterol 24S hydroxylase (Cyp46) levels in the rat brain. J Neurotrauma 2008;25:1087-1098.
182. Vega GL, Weiner MF, Lipton AM, Von Bergmann K, Lutjo-hann D, Moore C, Svetlik D. Reduction in levels of 24S-hydroxycholesterol by statin treatment in patients with Alzheimer disease. Arch Neurol 2003;60:510-515.
183. Accad M, Farese Jr. RV. Cholesterol homeostasis: a role for oxysterols. Curr Biol 1998;8:R601-R604.
184. Edwards PA, Ericsson J. Sterols and isoprenoids: signaling molecules derived from the cholesterol biosynthetic pathway. Annu Rev Biochem 1999;68:157-185.
185. Gueguen Y, Bertrand P, Ferrari L, Batt AM, Siest G. Control of apolipoprotein E secretion by 25-hydroxycholesterol and proinfl ammatory cytokines in the human astrocytoma cell line CCF-STTG1. Cell Biol Toxicol 2001;17:191-199.
186. Peet DJ, Janowski BA, Mangelsdorf DJ. The LXRs: a new class of oxysterol receptors. Curr Opin Genet Dev 1998;8:571-575.
187. Bjorkhem I, Lutjohann D, Diczfalusy U, Stahle L, Ahlborg G, Wahren J. Cholesterol homeostasis in human brain: turnover of 24S-hydroxycholesterol and evidence for a cerebral origin of most of this oxysterol in the circulation. J Lipid Res 1998;39:1594-1600.
188. Bretillon L, Lutjohann D, Stahle L, Widhe T, Bindl L, Egg-ertsen G, Diczfalusy U, Bjorkhem I. Plasma levels of 24S-hydroxycholesterol refl ect the balance between cerebral production and hepatic metabolism and are inversely related to body surface. J Lipid Res 2000;41:840-845.
189. Bjorkhem I, Heverin M, Leoni V, Meaney S, Diczfalusy U. Oxysterols and Alzheimer's disease. Acta Neurol Scand Suppl 2006;185:43-49.
190. Schonknecht P, Lutjohann D, Pantel J, Bardenheuer H, Hartmann T, von Bergmann K, Beyreuther K, Schroder J. Cerebrospinal fl uid 24S- hydroxycholesterol is increased in patients with Alzheimer's disease compared to healthy controls. Neurosci Lett 2002;324:83-85.
191. Bjorkhem I, Starck L, Andersson U, Lutjohann D, von Bahr S, Pikuleva I, Babiker A, Diczfalusy U. Oxysterols in the circulation of patients with the Smith-Lemli-Opitz syndrome: abnormal levels of 24S-and 27-hydroxycholesterol. J Lipid Res 2001;42:366-371.
192. Pfrieger F W. Outsourcing in the brain: do neurons depend on cholesterol delivery by astrocytes? Bioessays 2003;25:72-78.
193. Abildayeva K, Jansen PJ, Hirsch-Reinshagen V, Bloks VW, Bakker AH, Ramaekers FC, de Vente J, Groen AK, Wellington CL, Kuipers F, Mulder M. 24(S)-hydroxycholesterol participates in a liver X receptor-controlled pathway in astro-cytes that regulates apolipoprotein E-mediated cholesterol effl ux. J Biol Chem 2006;281:12799-12808.
194. Wong J, Quinn CM, Guillemin G, Brown AJ. Primary human astrocytes produce 24(S),25-epoxycholesterol with implications for brain cholesterol homeostasis. J Neurochem 2007;103:1764-1773.
195. Wong J, Quinn CM, Gelissen IC, Brown AJ. Endogenous 24(S),25- epoxycholesterol fi ne-tunes acute control of cellular cholesterol homeostasis. J Biol Chem 2008;283:700-707.
196. Laffi tte BA, Joseph SB, Walczak R, Pei L, Wilpitz DC, Collins JL, Tontonoz P. Autoregulation of the human liver X receptor alpha promoter. Mol Cell Biol 2001;21: 7558-7568.
197. Wang Y, Muneton S, Sjovall J, Jovanovic JN, Griffi ths WJ. The effect of 24S-hydroxycholesterol on cholesterol home-ostasis in neurons: quantitative changes to the cortical neuron proteome. J Proteome Res 2008;7:1606-1614.
198. Dietschy JM, Turley SD. Cholesterol metabolism in the brain. Curr Opin Lipidol 2001;12:105-112.
199. Bjorkhem I, Lutjohann D, Breuer O, Sakinis A, Wennmalm A. Importance of a novel oxidative mechanism for elimination of brain cholesterol. Turnover of cholesterol and 24(S)-hydroxycholesterol in rat brain as measured with 18O2 techniques in vivo and in vitro. J Biol Chem 1997;272: 30178-30184.
200. Bjorkhem I, Andersson U, Ellis E, Alvelius G, Ellegard L, Diczfalusy U, Sjovall J, Einarsson C. From brain to bile. Evidence that conjugation and omega-hydroxylation are important for elimination of 24S-hydroxycholesterol (cerebrosterol) in humans. J Biol Chem 2001;276:37004-37010.
201. Lutjohann D. Cholesterol metabolism in the brain: importance of 24S-hydroxylation. Acta Neurol Scand Suppl 2006;185:33-42.
202. Meaney S, Bodin K, Diczfalusy U, Bjorkhem I. On the rate of translocation in vitro and kinetics in vivo of the major oxysterols in human circulation: critical importance of the position of the oxygen function. J Lipid Res 2002;43: 2130-2135.
203. Raffai RL Weisgraber KH. Cholesterol: from heart attacks to Alzheimer's disease. J Lipid Res 2003;44:1423-1430.
204. Levesque G, Murthy MRV. Alzheimer's disease: what we have learned from gene analysis. In: Marwah J, Teitelbaum H, editors. Advances in neurodegenerative disorder. vol.2. Scottsdale, AZ: Prominent Press; 1998. p 49-70.
205. Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, Vogel FS, Hughes JP, van Belle G, Berg L. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropatho-logic assessment of Alzheimer's disease. Neurology 1991;41:479-486.
206. Burns M, Duff K. Cholesterol in Alzheimer's disease and tauopathy. Ann NY Acad Sci 2002;977:367-375.
207. Adair J. Cholesterol and neuropathologic markers of AD: a population-based autopsy study. Neurology 2002;59: 788-789; author reply 789.
208. Launer LJ, White LR, Petrovitch H, Ross GW, Curb JD. Cholesterol and neuropathologic markers of AD: a population-based autopsy study. Neurology 2001;57:1447-1452.
209. Arango D, Cruts M, Torres O, Backhovens H, Serrano ML, Villareal E, Montanes P, Matallana D, Cano C, Van Broeck-hoven C, Jacquier M. Systematic genetic study of Alzheimer disease in Latin America: mutation frequencies of the amyloid beta precursor protein and presenilin genes in Colombia. Am J Med Genet 2001;103:138-143.
210. Smith JD. Apolipoprotein E4: an allele associated with many diseases. Ann Med 2000;32:118-127.
211. Refolo LM, Malester B, LaFrancois J, Bryant-Thomas T, Wang R, Tint GS, Sambamurti K, Duff K, Pappolla MA. Hypercholesterolemia accelerates the Alzheimer's amyloid pathology in a transgenic mouse model. Neurobiol Dis 2000;7:321-331.
212. Cooper J. Dietary lipids in the aetiology of Alzheimer's disease: implications for therapy. Drugs Aging 2003;20: 399-418.
213. Blacker D, Haines JL, Rodes L, Terwedow H, Go RC, Har-rell LE, Perry RT, Bassett SS, Chase G, Meyers D, Albert MS, Tanzi R. ApoE-4 and age at onset of Alzheimer's disease: the NIMH genetics initiative. Neurology 1997;48: 139-147.
214. McGeer PL, Schulzer M, McGeer EG. Arthritis and anti-infl ammatory agents as possible protective factors for Alzheimer's disease: a review of 17 epidemiologic studies [see comments]. Neurology 1996;47:425-432.
215. Burns M, Duff K. Use of in vivo models to study the role of cholesterol in the etiology of Alzheimer's disease. Neuro-chem Res 2003;28:979-986.
216. Austen B, Christodoulou G, Terry JE. Relation between cholesterol levels, statins and Alzheimer's disease in the human population. J Nutr Health Aging 2002;6:377-382.
217. Hartmann T. Cholesterol, A beta and Alzheimer's disease. Trends Neurosci 2001;24:S45-S48.
218. Flirski M, Sobow T. Biochemical markers and risk factors of Alzheimer's disease. Curr Alzheimer Res 2005;2:47-64. (Pubitemid 41389259)
219. Notkola IL, Sulkava R, Pekkanen J, Erkinjuntti T, Ehnholm C, Kivinen P, Tuomilehto J, Nissinen A. Serum total cholesterol, apolipoprotein E epsilon 4 allele, and Alzheimer's disease. Neuroepidemiology 1998;17:14-20.
220. Sparks DL, Martins R, Martin T. Cholesterol and cognition: rationale for the AD cholesterol-lowering treatment trial and sex-related differences in beta-amyloid accumulation in the brains of spontaneously hypercholesterolemic Watanabe rabbits. Ann NY Acad Sci 2002;977:356-366.
221. Jarvik GP, Wijsman EM, Kukull WA, Schellenberg GD, Yu C, Larson EB. Interactions of apolipoprotein E genotype, total cholesterol level, age, and sex in prediction of Alzheimer's disease: a case-control study. Neurology 1995;45:1092-1096.
222. Lukiw WJ, Pappolla M, Pelaez RP, Bazan NG. Alzheimer's disease-a dysfunction in cholesterol and lipid metabolism. Cell Mol Neurobiol 2005;25:475-483.
223. Kivipelto M, Helkala EL, Laakso MP, Hanninen T, Hal-likainen M, Alhainen K, Soininen H, Tuomilehto J, Nissinen A. Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal, population based study. BMJ 2001;322:1447-1451.
224. Pappolla M A, Bryant-Thomas T K, Herbert D, Pacheco J, Fabra Garcia M, Manjon M, Girones X, Henry T L, Mat-subara E, Zambon D, Wolozin B, Sano M, Cruz-Sanchez F F, Thal L J, Petanceska S S and Refolo L M. Mild hyperc-holesterolemia is an early risk factor for the development of Alzheimer amyloid pathology. Neurology 2003;61:199-205.
225. Haley RW, Dietschy JM. Is there a connection between the concentration of cholesterol circulating in plasma and the rate of neuritic plaque formation in Alzheimer disease? Arch Neurol 2000;57:1410-1412.
226. Simons K, Ehehalt R. Cholesterol, lipid rafts, and disease. J Clin Invest 2002;110:597-603.
227. Simons M, Keller P, De Strooper B, Beyreuther K, Dotti CG, Simons K. Cholesterol depletion inhibits the generation of beta-amyloid in hippocampal neurons. Proc Natl Acad Sci USA 1998;95:6460-6464.
228. Wahrle S, Das P, Nyborg AC, McLendon C, Shoji M, Kawarabayashi T, Younkin LH, Younkin SG, Golde TE. Cholesterol-dependent gamma-secretase activity in buoyant cholesterol-rich membrane microdomains. Neurobiol Dis 2002;9:11-23.
229. Bogdanovic N, Bretillon L, Lund EG, Diczfalusy U, Lannfelt L, Winblad B, Russell DW, Bjorkhem I. On the turnover of brain cholesterol in patients with Alzheimer's disease. Abnormal induction of the cholesterol-catabolic enzyme CYP46 in glial cells. Neurosci Lett 2001;314:45-48.
230. Bretillon L, Siden A, Wahlund LO, Lutjohann D, Minthon L, Crisby M, Hillert J, Groth CG, Diczfalusy U, Bjorkhem I. Plasma levels of 24S-hydroxycholesterol in patients with neurological diseases. Neurosci Lett 2000;293:87-90.
231. Brown 3rd J, Theisler C, Silberman S, Magnuson D, Gotta-rdi-Littell N, Lee JM, Yager D, Crowley J, Sambamurti K, Rahman MM, Reiss AB, Eckman CB, Wolozin B. Differential expression of cholesterol hydroxylases in Alzheimer's disease. J Biol Chem 2004;279:34674-34681. (Pubitemid 39318097)
232. Famer D, Meaney S, Mousavi M, Nordberg A, Bjorkhem I, Crisby M. Regulation of alpha-and beta-secretase activity by oxysterols: cerebrosterol stimulates processing of APP via the alpha-secretase pathway. Biochem Biophys Res Comm 2007;359:46-50.
233. Ghribi O. Potential mechanisms linking cholesterol to Alzheimer's disease-like pathology in rabbit brain, hippocampal organotypic slices, and skeletal muscle. J Alzheimers Dis 2008;15:673-684.
234. Heverin M, Meaney S, Lutjohann D, Diczfalusy U, Wahren J, Bjorkhem I. Crossing the barrier: net fl ux of 27-hydroxycholesterol into the human brain. J Lipid Res 2005;46:1047-1052.
235. Scott Kim W, Chan SL, Hill AF, Guillemin GJ, Garner B. Impact of 27-hydroxycholesterol on amyloid-beta peptide production and ATP-binding cassette transporter expression in primary human neurons. J Alzheimers Dis 2009;16:121-131.
236. Sharma S, Prasanthi RPJ, Schommer E, Feist G, Ghribi O. Hypercholesterolemia-induced Abeta accumulation in rabbit brain is associated with alteration in IGF-1 signaling. Neurobiol Dis 2008;32:426-432.
237. Mateos L, Akterin S, Gil-Bea FJ, Spulber S, Rahman A, Bjorkhem I, Schultzberg M, Flores-Morales A, Cedazo-Minguez A. Activity-regulated cytoskeleton-associated protein in rodent brain is down-regulated by high fat diet in vivo and by 27-hydroxycholesterol in vitro. Brain Pathol 2009; 19:69-80.
238. Guzowski JF, Lyford GL, Stevenson GD, Houston FP, McGaugh JL, Worley PF, Barnes CA. Inhibition of activity-dependent arc protein expression in the rat hippocampus impairs the maintenance of long-term potentiation and the consolidation of long-term memory. J Neurosci 2000;20:3993-4001.
239. McIntyre CK, Miyashita T, Setlow B, Marjon KD, Steward O, Guzowski JF, McGaugh JL. Memory-infl uencing intra-ba-solateral amygdala drug infusions modulate expression of Arc protein in the hippocampus. Proc Natl Acad Sci USA 2005;102:10718-10723.
240. Ginsberg SD, Hemby SE, Lee VM, Eberwine JH, Tro-janowski JQ. Expression profi le of transcripts in Alzheimer's disease tangle-bearing CA1 neurons. Ann Neurol 2000;48:77-87.
241. Cutler RG, Kelly J, Storie K, Pedersen WA, Tammara A, Hatanpaa K, Troncoso JC, Mattson MP. Involvement of oxi-dative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease. Proc Natl Acad Sci USA 2004;101:2070-2075.
242. Wood WG, Schroeder F, Avdulov NA, Chochina SV, Igbav-boa U. Recent advances in brain cholesterol dynamics: transport, domains, and Alzheimer's disease. Lipids 1999;34:225-234.
243. Papassotiropoulos A, Lutjohann D, Bagli M, Locatelli S, Jessen F, Rao ML, Maier W, Bjorkhem I, von Bergmann K, Heun R. Plasma 24S-hydroxycholesterol: a peripheral indicator of neuronal degeneration and potential state marker for Alzheimer's disease. Neuroreport 2000;11:1959-1962.
244. Leoni V, Shafaati M, Salomon A, Kivipelto M, Bjorkhem I, Wahlund LO. Are the CSF-levels of 24S-hydroxycholesterol a sensitive biomarker for mild cognitive impairment? Neu-rosci Lett 2006;397:83-87.
245. Sidera C, Parsons R, Austen B. Proteolytic cascade in the amyloidogenesis of Alzheimer's disease. Biochem Soc Trans 2004;32:33-36.
246. Papassotiropoulos A, Streffer JR, Tsolaki M, Schmid S, Thal D, Nicosia F, Iakovidou V, Maddalena A, Lutjohann D, Ghe-bremedhin E, Hegi T, Pasch T, Traxler M, Bruhl A, Benussi L, Binetti G, Braak H, Nitsch RM, Hock C. Increased brain beta-amyloid load, phosphorylated tau, and risk of Alzheimer disease associated with an intronic CYP46 polymorphism. Arch Neurol 2003;60:29-35.
247. Ferrera P, Mercado-Gomez O, Silva-Aguilar M, Valverde M, Arias C. Cholesterol potentiates beta-amyloid-induced tox-icity in human neuroblastoma cells: involvement of oxidative stress. Neurochem Res 2008;33:1509-1517.
248. Kolsch H, Lutjohann D, Tulke A, Bjorkhem I, Rao ML. The neurotoxic effect of 24-hydroxycholesterol on SH-SY5Y human neuroblastoma cells. Brain Res 1999;818:171-175.
249. Hureau C, Faller P. Abeta-mediated ROS production by Cu ions: structural insights, mechanisms and relevance to Alzheimer's disease. Biochimie 2009;91:1212-1217.
250. Dong J, Atwood CS, Anderson VE, Siedlak SL, Smith MA, Perry G, Carey PR. Metal binding and oxidation of amyloid-beta within isolated senile plaque cores: Raman microscopic evidence. Biochemistry 2003;42:2768-2773.
251. Naslund J, Schierhorn A, Hellman U, Lannfelt L, Roses AD, Tjernberg LO, Silberring J, Gandy SE, Winblad B, Green-gard P, Nordstedt C, Terenius L. Relative abundance of Alzheimer A beta amyloid peptide variants in Alzheimer disease and normal aging. Proc Natl Acad Sci USA 1994;91:8378-8382.
252. Kuo YM, Kokjohn TA, Beach TG, Sue LI, Brune D, Lopez JC, Kalback WM, Abramowski D, Sturchler-Pierrat C, Staufen-biel M, Roher AE. Comparative analysis of amyloid-beta chemical structure and amyloid plaque morphology of trans-genic mouse and Alzheimer's disease brains. J Biol Chem 2001;276:12991-12998.
253. Bassett CN, Montine TJ. Lipoproteins and lipid peroxida-tion in Alzheimer's disease. J Nutr Health Aging 2003;7:24-29.
254. Gibson WW, Eckert GP, Igbavboa U, Muller WE. Amyloid beta-protein interactions with membranes and cholesterol: causes or casualties of Alzheimer's disease. Biochim Biophys Acta 2003;1610:281-290.
255. Michikawa M, Fan QW, Isobe I, Yanagisawa K. Apolipopro-tein E exhibits isoform-specifi c promotion of lipid effl ux from astrocytes and neurons in culture. J Neurochem 2000;74:1008-1016.
256. Koudinov AR, Koudinova N V. Essential role for cholesterol in synaptic plasticity and neuronal degeneration. FASEB J 2001;314:1858-1860.
257. Fan QW, Yu W, Gong JS, Zou K, Sawamura N, Senda T, Yanagisawa K, Michikawa M. Cholesterol-dependent modulation of dendrite outgrowth and microtubule stability in cultured neurons. J Neurochem 2002;80:178-190.
258. Michikawa M. The role of cholesterol in pathogenesis of Alzheimer's disease: dual metabolic interaction between amyloid beta-protein and cholesterol. Mol Neurobiol 2003;27:1-12.
259. Gong JS, Kobayashi M, Hayashi H, Zou K, Sawamura N, Fujita SC, Yanagisawa K, Michikawa M. Apolipoprotein E (ApoE) isoform-dependent lipid release from astrocytes prepared from human ApoE3 and ApoE4 knock-in mice. J Biol Chem 2002;277:29919-29926.
260. Poirier J. Apolipoprotein E and cholesterol metabolism in the pathogenesis and treatment of Alzheimer's disease. Trends Mol Med 2003;9:94-101.
261. Poirier J. Apolipoprotein E4, cholinergic integrity and the pharmacogenetics of Alzheimer's disease. J Psychiatry Neu-rosci 1999;24:147-153. (Pubitemid 29198120)
262. Pfrieger F W. Cholesterol homeostasis and function in neurons of the central nervous system. Cell Mol Life Sci 2003;60:1158-1171.
263. Takemoto M, Liao JK. Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors. Arterioscler Thromb Vascular Biol 2001;21:1712-1719.
264. Kinlay S, Libby P, Ganz P. Endothelial function and coronary artery disease. Curr Opin Lipidol 2001;12:383-389.
265. Rauch U, Osende JI, Chesebro JH, Fuster V, Vorchheimer DA, Harris K, Harris P, Sandler DA, Fallon JT, Jayaraman S, Badimon JJ. Statins and cardiovascular diseases: the multiple effects of lipid-lowering therapy by statins. Atherosclerosis 2000;153:181-189.
266. Farmer JA, Torre-Amione G. Comparative tolerability of the HMG-CoA reductase inhibitors. Drug Saf 2000;23: 197-213.
267. Joukhadar C, Klein N, Prinz M, Schrolnberger C, Vukovich T, Wolzt M, Schmetterer L, Dorner G T. Similar effects of ator-vastatin, simvastatin and pravastatin on thrombogenic and infl ammatory parameters in patients with hypercholestero-lemia. Thromb Haemost 2001;85:47-51.
268. Simons M, Keller P, Dichgans J, Schulz JB. Cholesterol and Alzheimer's disease: is there a link? Neurology 2001;57:1089-1093.
269. Scott HD, Laake K. Statins for the prevention of Alzheimer's disease. Cochrane database of systematic reviews (Online) 2001;4:CD003160.
270. Scott HD, Laake K. Statins for the reduction of risk of Alzheimer's disease. Cochrane database of systematic reviews (Online) 2001;3:CD003160.
271. Wolozin B, Kellman W, Ruosseau P, Celesia GG, Siegel G. Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. Arch Neurol 2000;57:1439-1443.
272. Bales KR, Verina T, Cummins DJ, Du Y, Dodel RC, Saura J, Fishman CE, DeLong CA, Piccardo P, Petegnief V, Ghetti B, Paul SM. Apolipoprotein E is essential for amyloid deposition in the APP(V717F) transgenic mouse model of Alzheimer's disease. Proc Natl Acad Sci USA 1999;96:15233-15238.
273. Fassbender K, Simons M, Bergmann C, Stroick M, Lutjo-hann D, Keller P, Runz H, Kuhl S, Bertsch T, von Bergmann K, Hennerici M, Beyreuther K, Hartmann T. Simvastatin strongly reduces levels of Alzheimer's disease beta-amyloid peptides Abeta 42 and Abeta 40 in vitro and in vivo. Proc Natl Acad Sci USA 2001;98:5856-5861.
274. Jick H, Zornberg GL, Jick SS, Seshadri S, Drachman DA. Statins and the risk of dementia. Lancet 2000;356:1627-1631.
275. Cucchiara B, Kasner SE. Use of statins in CNS disorders. J Neurol Sci 2001;187:81-89.
276. Fassbender K, Stroick M, Bertsch T, Ragoschke A, Kuehl S, Walter S, Walter J, Brechtel K, Muehlhauser F, Von Berg-mann K, Lutjohann D. Effects of statins on human cerebral cholesterol metabolism and secretion of Alzheimer amyloid peptide. Neurology 2002;59:1257-1258.
277. Friedhoff LT, Cullen EI, Geoghagen NS, Buxbaum JD. Treatment with controlled-release lovastatin decreases serum concentrations of human beta-amyloid (A beta) peptide. Int J Neuropsychopharmacol 2001;4:127-130.
278. Petanceska SS, DeRosa S, Olm V, Diaz N, Sharma A, Thomas-Bryant T, Duff K, Pappolla M, Refolo LM. Statin therapy for Alzheimer's disease: will it work? J Mol Neurosci 2002;19:155-161.
279. Sjogren M, Gustafsson K, Syversen S, Olsson A, Edman A, Davidsson P, Wallin A, Blennow K. Treatment with simvas-tatin in patients with Alzheimer's disease lowers both alpha-and beta-cleaved amyloid precursor protein. Dement Geriatr Cogn Disord 2003;16:25-30.
280. Kostis JB, Rosen RC, Wilson AC. Central nervous system effects of HMG CoA reductase inhibitors: lovastatin and prav-astatin on sleep and cognitive performance in patients with hypercholesterolemia. J Clin Pharmacol 1994;34:989-996.
281. Locatelli S, Lutjohann D, Schmidt HH, Otto C, Beisiegel U, von Bergmann K. Reduction of plasma 24S-hydroxycholes-terol (cerebrosterol) levels using high-dosage simvastatin in patients with hypercholesterolemia: evidence that simvasta-tin affects cholesterol metabolism in the human brain. Arch Neurol 2002;59:213-216.
282. Simons M, Schwarzler F, Lutjohann D, von Bergmann K, Beyreuther K, Dichgans J, Wormstall H, Hartmann T, Schulz JB. Treatment with simvastatin in normocholesterolemic patients with Alzheimer's disease: a 26-week randomized, placebo-controlled, double-blind trial. Ann Neurol 2002; 52:346-350.
283. Crisby M, Carlson LA, Winblad B. Statins in the prevention and treatment of Alzheimer disease. Alzheimer Dis Assoc Disord 2002;16:131-136.
284. Andrée P, Dallner G, Ernster L. Ubiquinol: an endogenous lipid-soluble antioxidant in animal tissues. In: Ozben T, editor. Free radicals, oxidative stress and antioxidants: Pathological and physiological signifi cance. New York: Plenum Publishng Corporation; 1998. p 293-314.
285. Ernster L, Dallner G. Biochemical, physiological and medical aspects of ubiquinone function. Biochim Biophys Acta 1995;1271:195-204.
286. Sparks DL, Connor DJ, Browne PJ, Lopez JE, Sabbagh MN. HMG-CoA reductase inhibitors (statins) in the treatment of Alzheimer's disease and why it would be ill-advised to use one that crosses the blood-brain barrier. J Nutr Health Aging 2002;6:324-331.
287. Vega GL, Weiner MF. Plasma 24S hydroxycholesterol response to statins in Alzheimer's disease patients: effects of gender, CYP46, and ApoE polymorphisms. J Mol Neurosci 2007;33:51-55.
288. Wolozin B, Manger J, Bryant R, Cordy J, Green RC, McKee A. Re-assessing the relationship between cholesterol, statins and Alzheimer's disease. Acta Neurol Scand Suppl 2006;185:63-70.
289. Repa JJ, Li H, Frank-Cannon TC, Valasek MA,Turley SD, Tansey MG, Dietschy JM. Liver X receptor activation enhances cholesterol loss from the brain, decreases neuroin-fl ammation, and increases survival of the NPC1 mouse. J Neurosci 2007;27:14470-14480.
290. Sparks DL, Sabbagh MN, Connor DJ, Lopez JE, Launer LJ, Browne PJ, Wasser D, Johnson-Traver S, Lochhead J, Ziol-wolski C. Atorvastatin for the treatment of mild to moderate Alzheimer disease: preliminary results. Arch Neurol 2005;62:753-757.
291. Thelen KM, Lutjohann D, Vesalainen R, Janatuinen T, Knu-uti J, von Bergmann K, Lehtimaki T, Laaksonen R. Effect of pravastatin on plasma sterols and oxysterols in men. Eur J Clin Pharmacol 2006;62:9-14.
292. Kivipelto M, Laakso MP, Tuomilehto J, Nissinen A, Soininen H. Hypertension and hypercholesterolaemia as risk factors for Alzheimer's disease: potential for pharmacological intervention. CNS Drugs 2002;16:435-444.
293. Golde TE, Eckman CB. Cholesterol modulation as an emerging strategy for the treatment of Alzheimer's disease. Drug Discov Today 2001;6:1049-1055.
294. Kandutsch AA, Chen HW, Heiniger HJ. Biological activity of some oxygenated sterols. Science 1978;201:498-501.
295. Barish GD. Peroxisome proliferator-activated receptors and liver X receptors in atherosclerosis and immunity. J Nutr 2006;136:690-694.
296. Arai S, Shelton JM, Chen M, Bradley MN, Castrillo A, Bookout AL, Mak PA, Edwards PA, Mangelsdorf DJ, Ton-tonoz P, Miyazaki T. A role for the apoptosis inhibitory factor AIM/Spalpha/Api6 in atherosclerosis development. Cell Metab 2005;1:201-213.
297. Joseph SB, Bradley MN, Castrillo A, Bruhn KW, Mak PA, Pei L, Hogenesch J, O'Connell RM, Cheng G, Saez E, Miller JF. Tontonoz P. LXR-dependent gene expression is important for macrophage survival and the innate immune response. Cell 2004;119:299-309.
298. Blaschke F, Leppanen O, Takata Y, Caglayan E, Liu J, Fish-bein MC, Kappert K, Nakayama KI, Collins AR, Fleck E, Hsueh WA, Law RE, Bruemmer D. Liver X receptor agonists suppress vascular smooth muscle cell proliferation and inhibit neointima formation in balloon-injured rat carotid arteries. Circulat Res 2004;95:e110-e123.
299. Levin N, Bischoff ED, Daige CL, Thomas D, Vu CT, Hey-man RA, Tangirala RK, Schulman IG. Macrophage liver X receptor is required for antiatherogenic activity of LXR agonists. Arterioscler Thromb Vasc Biol 2005;25:135-142.
300. Ohtsuka M, Miyashita Y, Shirai K. Lipids deposited in human atheromatous lesions induce apoptosis of human vascular smooth muscle cells. J Atheroscler Thromb 2006;13:256-262.
301. Tabas I. Consequences and therapeutic implications of mac-rophage apoptosis in atherosclerosis: the importance of lesion stage and phagocytic effi ciency. Arterioscler Thromb Vasc Biol 2005;25:2255-2264.
302. 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.
303. Adams CM, Reitz J, De Brabander JK, Feramisco JD, Li L, Brown MS, Goldstein JL. Cholesterol and 25-hydroxycho-lesterol inhibit activation of SREBPs by different mechanisms, both involving SCAP and Insigs. J Biol Chem 2004;279:52772-52780.
304. Goldstein JL, DeBose-Boyd RA, Brown MS. Protein sensors for membrane sterols. Cell 2006;124:35-46.
305. 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.
306. Lu TT, Repa JJ, Mangelsdorf DJ. Orphan nuclear receptors as eLiXiRs and FiXeRs of sterol metabolism. J Biol Chem 2001;276:37735-37738.
307. Chawla A, Repa JJ, Evans RM, Mangelsdorf DJ. Nuclear receptors and lipid physiology: opening the X-fi les. Science 2001;294:1866-1870.
308. Peet DJ, Turley SD, Ma W, Janowski BA, Lobaccaro JM, Hammer RE, Mangelsdorf DJ. Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxys-terol receptor LXR alpha. Cell 1998;93:693-704.
309. Tu H, Okamoto AY, Shan B. FXR, a bile acid receptor and biological sensor. Trends Cardiovasc Med 2000;10:30-35.
310. Lu TT, Makishima M, Repa JL, Schoonjans K, Kerr TA, Auwerx J, Mangelsdorf DJ. Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors. Mol Cell 2000;6:507-515.
311. Graf GA, Li WP, Gerard RD, Gelissen I, White A, Cohen JC, Hobbs HH. Coexpression of ATP-binding cassette proteins ABCG5 and ABCG8 permits their transport to the apical surface. J Clin Invest 2002;110:659-669.
312. Yu L, Hammer RE, Li-Hawkins J, Von Bergmann K, Lutjo-hann D, Cohen JC, Hobbs HH. Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion. Proc Natl Acad Sci USA 2002;99:16237-16242.
313. Berge KE, Tian H, Graf GA, Yu L, Grishin NV, Schultz J, Kwiterovich P, Shan B, Barnes R, Hobbs HH. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science 2000; 290:1771-1775.
314. Plosch T, Bloks VW,Terasawa Y, Berdy S, Siegler K, Van Der Sluijs F, Kema IP, Groen AK, Shan B, Kuipers F, Schwarz M. Sitosterolemia in ABC-transporter G5-defi cient mice is aggravated on activation of the liver-X receptor. Gastroen-terology 2004;126:290-300.
315. Yu L, Li-Hawkins J, Hammer RE, Berge KE, Horton JD, Cohen JC, Hobbs HH. Overexpression of ABCG5 and ABCG8 promotes biliary cholesterol secretion and reduces fractional absorption of dietary cholesterol. J Clin Invest 2002;110:671-680.
316. Gregg RE, Connor WE, Lin DS, Brewer Jr HB. Abnormal metabolism of shellfi sh sterols in a patient with sitosterolemia and xanthomatosis. J Clin Invest 1986;77:1864-1872.
317. Lee MH, Lu K, Patel SB. Genetic basis of sitosterolemia. Curr Opin Lipidol 2001;12:141-149.
318. Lu K, Lee MH, Patel SB. Dietary cholesterol absorption; more than just bile. Trends Endocrinol Metab TEM 2001;12:314-320.
319. Salen G, Shefer S, Nguyen L, Ness GC, Tint GS, Shore V. Sitosterolemia. J Lipid Res 1992;33:945-955.
320. Lee MH, Lu K, Hazard S, Yu H, Shulenin S, Hidaka H, Kojima H, Allikmets R, Sakuma N, Pegoraro R, Srivastava AK, Salen G, Dean M, Patel SB. Identifi cation of a gene, ABCG5, important in the regulation of dietary cholesterol absorption. Nature Genet 2001;27:79-83.
321. Tauscher A, Kuver R. ABCG5 and ABCG8 are expressed in gallbladder epithelial cells. Biochem Biophys Res Comm 2003;307:1021-1028.
322. Tam SP, Mok L, Chimini G, Vasa M, Deeley RG. ABCA1 mediates high-affi nity uptake of 25-hydroxycholesterol by membrane vesicles and rapid effl ux of oxysterol by intact cells. Am J Physiol Cell Physiol 2006;291:C490-C502.
323. McNeish J, Aiello RJ, Guyot D, Turi T, Gabel C, Aldinger C, Hoppe KL, Roach ML, Royer LJ, de Wet J, Broccardo C, Chimini G, Francone OL. High density lipoprotein defi-ciency and foam cell accumulation in mice with targeted disruption of ATP-binding cassette transporter-1. Proc Natl Acad Sci USA 2000;97:4245-4250.
324. Groen AK, Bloks VW, Bandsma RH, Ottenhoff R, Chimini G, Kuipers. F. Hepatobiliary cholesterol transport is not impaired in Abca1-null mice lacking HDL. J Clin Invest 2001;108:843-850.
325. Drobnik W, Lindenthal B, Lieser B, Ritter M, Christiansen Weber T, Liebisch G, Giesa U, Igel M, Borsukova H, Buchler C, Fung-Leung WP, Von Bergmann K, Schmitz G. ATP-binding cassette transporter A1 (ABCA1) affects total body sterol metabolism. Gastroenterology 2001;120: 1203-1211.
326. Mulligan JD, Flowers MT, Tebon A, Bitgood JJ, Wellington C, Hayden MR, Attie AD. ABCA1 is essential for effi cient baso-lateral cholesterol effl ux during the absorption of dietary cholesterol in chickens. J Biol Chem 2003;278:13356-13366.
327. Field FJ, Born E, Mathur SN. LXR/RXR ligand activation enhances basolateral effl ux of beta-sitosterol in CaCo-2 cells. J Lipid Res 2004;45:905-913.
328. Klett EL, Lu K, Kosters A, Vink E, Lee MH, Altenburg M, Shefer S, Batta AK, Yu H, Chen J, Klein R, Looije N, Oude-Elferink R, Groen AK, Maeda N, Salen G, Patel SB. A mouse model of sitosterolemia: absence of Abcg8/sterolin-2 results in failure to secrete biliary cholesterol. BMC Med 2004;2:5.
329. Graf GA, Yu L, Li WP, Gerard R, Tuma PL, Cohen JC, Hobbs HH. ABCG5 and ABCG8 are obligate heterodimers for protein traffi cking and biliary cholesterol excretion. J Biol Chem 2003;278:48275-48282.