Current drug targets for antihyperlipidemic therapy

Mini-Reviews in Medicinal Chemistry

Volumn 10, Issue 3, 2010, Pages 232-262

  Jain, Kishor S ^a   Kulkarni, Ranganath R ^a   Jain, Dilpesh P ^a  

^a SINHGAD COLLEGE OF PHARMACY   (India)

Author keywords

Antiatherogenic; Antihyperlipidemic; Drug targets; Reverse cholesterol transport

Indexed keywords

2, 2 DIMETHYL N (2, 4, 6 TRIMETHOXYPHENYL) DODECANAMIDE; 2,2 DIMETHYL N (2,4,6 TRIMETHOXYPHENYL)DODECANAMIDE; [2 METHYL 4 [4 METHYL 2 (4 TRIFLUOROMETHYLPHENYL) 5 THIAZOLYLMETHYLTHIO] PHENOXY] ACETIC ACID; [2 METHYL 4 [4 METHYL 2 (4 TRIFLUOROMETHYLPHENYL) 5 THIAZOLYLMETHYLTHIO]PHENOXY]ACETIC ACID; ADENOSINE TRIPHOSPHATE CITRATE LYASE; ALPHA TOCOPHEROL; ANTILIPEMIC AGENT; ANTIOXIDANT; APOLIPOPROTEIN E; AVASIMIBE; AZALANSTAT; C REACTIVE PROTEIN; CHOLESTEROL ESTER TRANSFER PROTEIN; CHYLOMICRON; DIACYLGLYCEROL ACYLTRANSFERASE; EFLUCIMIBE; EZETIMIBE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HYDROXYMETHYLGLUTARYL COENZYME A SYNTHASE; LANOSTEROL SYNTHASE; LOW DENSITY LIPOPROTEIN CHOLESTEROL; MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR AGONIST; PROBUCOL; RESVERATROL; SQUALENE MONOOXYGENASE; SQUALENE SYNTHASE; STEROL 14ALPHA DEMETHYLASE; STEROL REGULATORY ELEMENT BINDING PROTEIN; UBIDECARENONE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VERY LOW DENSITY LIPOPROTEIN CHOLESTEROL; CARRIER PROTEIN; CHOLESTEROL ACYLTRANSFERASE; DRUG DERIVATIVE; LIPOPROTEIN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; UBIQUINONE;

ABSORPTION; ANTIFUNGAL ACTIVITY; ANTIINFLAMMATORY ACTIVITY; ATHEROSCLEROSIS; CHOLESTEROL SYNTHESIS; CLINICAL TRIAL (TOPIC); DRUG BINDING; DRUG TARGETING; ENZYME INHIBITION; HEART DISEASE; HUMAN; HYPERCHOLESTEROLEMIA; HYPERLIPIDEMIA; LIPID METABOLISM; LIPID OXIDATION; MICROSOME; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN METABOLISM; REVIEW; SIGNAL TRANSDUCTION; CHEMISTRY; DRUG ANTAGONISM; METABOLISM;

ANTILIPEMIC AGENTS; ATP CITRATE (PRO-S)-LYASE; C-REACTIVE PROTEIN; CARRIER PROTEINS; CHOLESTEROL ESTER TRANSFER PROTEINS; HUMANS; HYPERLIPIDEMIAS; LIPOPROTEINS; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS; STEROL O-ACYLTRANSFERASE; UBIQUINONE;

EID: 77954743805     PISSN: 13895575     EISSN: 18755607     Source Type: Journal    
DOI: 10.2174/138955710791185037     Document Type: Review

References (297)

1. Rosamond, W.D.; Chambless, L.E.; Folsom, A.R.; Cooper, L.S.; ConWill, D.E.; Clegg, L.; Wang, C.H.; Heiss, G. Trends in the incidence of myocardial infarction and in mortality due to coronary heart disease, 1987 to 1994. N. Eng. J. Med., 1998, 339, 861-867.
2. Murray, C.J.L.; Lopez, A.D. Mortality by cause for eight regions of the world: Global Burden of Disease Study. Lancet, 1997, 349, 1269-1276.
3. McGill, H.C. Jr. Geographical Pathology of Atheroslclerosis, Williams and Wilken Co: Baltimore, 1985.
4. Overturf, M.L.; Loose-Mitchell, D.S. In vivo model systems: the choice of the experimental animal model for analysis of lipoproteins and atherosclerosis. Curr. Opin. Lipidol., 1992, 3, 179-185.
5. Ghatak, A.; Asthana, O. Recent Trends in Hyperlipoproteinemias and its Pharmacotherapy. Indian J. Pharmacol., 1995, 27, 14-29.
6. Schwandt, P. Triglyceride-rich lipoproteins as risk factors for atherosclerosis. Klin. Wochenschr., 1990, 68, 54-8.
7. www.hvif.com. (This home page belongs to The Heart and Vascular Institute of Florida, are new frontiers of cardiovascular care and treatment through advances in nuclear medicine, cutting edge technology and research, and the development of preventive and educational services).
8. http://www.clinicalcardiology.org/supplements/CC26S1/supplement_1_03.pdf. (Clinical Cardiology provides a forum for the coordination of clinical research in cardiology and cardiovascular surgery).
9. Kannel, W.B.; Castelli, W.P.; Gordon, T.; McNamara, P.M. Serum cholesterol, lipoproteins, and the risk of coronary heart disease. The Framingham Study. Ann. Intern. Med., 1971, 74, 1-12.
10. http://www.preventive-cardiology.com/lipoprotein%20a.htm. (This website belongs to Preventive Cardiology of Victoria, developed to prevent atherosclerosis which is without question the most common cause of death in the developed world).
11. Beisiegel, U. Lipoprotein metabolism. Eur. Heart. J., 1998, 19, A20.
12. Nilsson-Ehle, P.; Garfinkel, A.S.; Schotz, M.C. Lipolytic Enzymes and Plasma Lipoprotein Metabolism. Ann. Rev. Biochem., 1980, 49, 667-693.
13. Kubo, M.; Matsuzawa, Y.; Yokoyama, S.; Tajima, S.; Ishikawa, K.; Yamamoto, A.; Tarui, S. Mechanism of inhibition of hepatic triglyceride lipase from human postheparin plasma by apolipoproteins A-I and A-II. J. Biochem., 1982, 92, 865-870.
14. Peelman, F.; Vandekerckhove J.; Rosseneu, M. Structure and function of lecithin cholesterol acyl transferase: new insights from structural predictions and animal models. Curr. Opin. Lipidol., 2000, 11, 155-160.
15. Brewer, H.B. High-density lipoproteins: a new potential therapeutic target for the prevention of cardiovascular disease. Arterioscler. Throm. Vasc. Biol., 2004, 24, 387-391.
16. Olofsson, S.O.; Aap, L.; Boren, J. The assembly and secretion of apolipoprotein B-containing lipoproteins. Curr. Opin. Lipidol., 1999, 10, 341-346.
17. Chang, C.C.; Huh, H.Y.; Cadigan, K.M.; Chang, T.Y. Molecular cloning and functional expression of human acyl-coenzyme A:cholesterol acyltransferase cDNA in mutant Chinese hamster ovary cells. J. Biol.Chem., 1993, 268, 20747-20755.
18. Fleming, R.M. The Pathogenesis of Vascular Disease. Springer- Verlag: New York, 1999.
19. David K.; Spady, D.K. reverse cholesterol transport and atherosclerosis regression. Circulation., 1999, 100, 576-578.
20. VanHeek, M.; Davis, H. Pharmacology of ezetimibe. Eur. Heart J., 2002, 4, J5-J8.
21. Bays, H. Ezetimibe. Expert Opin. Investig. Drugs, 2002, 11, 1587-1604.
22. Liang, G.; Jing, W.; Wei, Q.; Hong-Hua, M.; Jian, C.; Yu-Xiu, Q.; Bo-Liang L.; Bao-Liang, S. Ezetimibe blocks internalization of the npc1l1/cholesterol complex. Cell Metab., 2008, 7, 469-471.
23. Altmann, S.W.; Davis, H.R.; Zhu, L.J.; Yao, X.R.; Hoos, L.M.; Tetzloff, J.; Iyer, S.P.N.; Maguire, M.; Golovko, A.; Zene, M.; Wang, L.Q.; Murgolo, N.; Graziano, M.P. Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science, 2004, 303, 1201-1204.
24. Yamagishi, S.; Nakamura, K.; Matsui, T.; Sato, T.; Takeuchi, M. Inhibition of intestinal cholesterol absorption by ezetimibe is a novel therapeutic target for fatty liver. Med. Hypotheses, 2006, 66, 844-846.
25. Sudhop, T.; Lutjohann, D.; Kodal, A.; Michael, I.; Diane, L.T.; Shah, S.; Perevozskaya, I.; Bergmann, K. Inhibition of intestinal cholesterol absorption by ezetimibe in humans. Circulation, 2002, 106, 1943-1948.
26. Kosoglou, T.; Statkevich, P.; Johnson-Leconas, A.O.; Paolini, J.F.; Bergman, A.J.; Atlon, K.B. Ezetimibe: A review of its metabolism, pharmacokinetics and drug interactions. Clin. Pharmacokinet., 2005, 44, 467-494.
27. Davis, H.R.; Zhu, L.J.; Hoss, L.M.; Tetzloff, G.; Maguire, M.; Liu, J.; Yao, X.; Iyer, S.P.N.; Lam, M.H.; Lund, E.G.; Detman, P.A.; Graziano, M.P.; Altmann, S.W. Niemann-Pick C1 Like 1 (NPC1L1) is the intestinal phytosterol and cholesterol transporter and a key modulator of whole-body cholesterol homeostasis. J. Biol. Chem., 2004, 297, 33586-33592.
28. Kvaerno, L.; Werder, M.; Hauser, H.; Erick, M.C. Synthesis and in vitro evaluation of inhibitors of intestinal cholesterol absorption. J. Med. Chem., 2005, 48, 6035-6053.
29. Mewshaw, R.A.; Commons, J.; Strike, D.P. EP 428385A, 1991.
30. Krause, B.R.; Sliskovis, Dr.; Anderson, M.; Homan, R. Lipidlowering effects of way-121898, an inhibitor of pancreatic cholesteryl ester hydrolase. Lipids, 1998, 33, 489-498.
31. Chawla, A.; Repa, J.J.; Evans, R.M.; Mangelsdorf, D.J. Nuclear receptors and lipid physiology: opening the X-files. Science, 2001, 294, 1866-1870.
32. Berger, J.; Moller, D.E. The mechanisms of action of PPARS. Annu. Rev. Med., 2002, 53, 409-435.
33. Barbier, O.; Torra, I.P.; Duguay, Y. Pleiotropic actions of peroxisome proliferator-activated receptors in lipid metabolism and atherosclerosis. Arterioscler. Thromb. Vasc. Biol., 2002, 22, 717-726.
34. Duez, H.; Chao, Y.S.; Hernandez, M. Reduction of Atherosclerosis by the Peroxisome Proliferator-activated Receptor α Agonist Fenofibrate in Mice. J. Biol. Chem., 2002, 277, 48051-48057.
35. Li, A.C.; Brown, K.K.; Silvestre, M.J.; Willson, T.M.; Palinski, W.; Christopher K. Glass, C.K. Peroxisome proliferator-activated receptor γ ligands inhibit development of atherosclerosis in LDL receptor-deficient mice. J. Clin. Invest., 2000, 106, 523-531.
36. Kang, K.; Hatano, B.; Lee, C.-H. PPARδ agonists and metabolic diseases. Curr. Atheroscler Rep., 2007, 9, 72-77.
37. Lee, C.H.; Chawla, A.; Urbiztondo, D. Liao, D.; Boisvert, W.A.; Evans, R.M. Transcriptional repression of atherogenic inflammation: modulation by PPARdelta. Science, 2003, 302, 453-457.
38. -/- mice. Atherosclerosis, 2005, 181, 29-37.
39. Barish, G.D.; Atkins, A.R.; Downes, M.; Olson, P.; Chong, L.W.; Nelson, M.; Zou, Y.; Hwang, H.; Kang, H.; Curtiss, L.; Evans, R.M.; Lee, C.H. PPARδ regulates multiple proinflammatory pathways to suppress atherosclerosis. Proc. Natl. Acad. Sci. USA, 2008, 105, 4271-4276.
40. Takata, Y.; Liu, J.; F. Yin.; Collins, A.R.; Lyon, C.J.; Lee, C.H.; Atkins, A.R.; Downes, M.; Barish, G.D.; Evans, R.M.; Hsueh, W.A.; Tangirala, R.K. PPARδ-mediated anti-inflammatory mechanisms inhibit angiotensin II-accelerated atherosclerosis. Proc. Natl. Acad. Sci. USA, 2008, 105, 4277-4282.
41. Takero, N.; Naoki, T.; Eiko, S.; Yuji, K.; Atsushi, H.; Rui, H.; Gang, Li.; Yufeng, Li.; Kozo, N.; Frank, J.; G.; Toshifumi, A. Cholesterol-lowering effect of bezafibrate is independent of peroxisome proliferator-activated receptor activation in mice. Biochem. Pharmacol., 2008, 8, 1-12.
42. Tachibana, K.; Kobayashi, Y.; Tanaka, T.; Tagami, M.; Sugiyama, A.; Katayama, T.; Ueda, C.; Yamasaki, D.; Ishimoto, K.; Sumitomo, M.; Uchiyama, Y.; Kohro, T.; Sakai, J.; Hamakubo, T.; Kodama, T.; Doi, T. Gene expression profiling of potential peroxisome proliferator-activated receptor (PPAR) target genes in human hepatoblastoma cell lines inducibly expressing different PPAR isoforms. Nucl. Recept., 2005, 3, 1-17.
43. Sakashita, N.; Akira Miyazaki, A.; Takeya, M.; Horiuchi, S.; Chang, C.C.Y.; Ta-Yuan Chang, T.-Y.; Takahashi, K. Localization of human acyl-coenzyme a:cholesterol acyltransferase-1 (acat-1) in macrophages and in various tissues. American. J. Pathol., 2000, 156, 227-236.
44. Lee, R.G.; Willingham, M.C.; Davis, M.A.; Skinner, K.A.; Rudel, L.L. Differential expression of ACAT1 and ACAT2 among cells within liver, intestine, kidney, and adrenal of nonhuman primates. J. Lipid Res., 2000, 41, 1991-2001.
45. Sliskovic, D.R.; White, A.D. therapeutic potential of acat inhibitors as lipid lowering and anti atherosclerotic agents. Trends. Pharmacol. Sci., 1991, 12,194-199.
46. Thomas, M.A.; Bocan, B.R.; Krause, W.S.; Rosebury, Sandra, B.M.; Xiaokang, Lu.; Catherine, D.; Terry, M.; Chetan, L.; Helen, L. The ACAT inhibitor avasimibe reduces macrophages and matrix metalloproteinase expression in atherosclerotic lesions of hypercholesterolemic rabbits. Arterioscler. Thromb. Vasc. Biol., 2000, 20, 70-79.
47. Lopez-Farre, A.J.; Sacristan, D.; Zamorano-Leon, J.J.; San-Martin, N.; Macaya, C. Inhibition of Acyl-CoA cholesterol acyltransferase by F12511 (Eflucimibe): could it be a new antiatherosclerotic therapeutic?. Cardiovasc. Drug. Rev., 2008, 26, 65-74.
48. Roth, B.D.; Blankley, C.J.; Hoe, M.L.; Holmes, A.; Roark, W.H.; Trivedi, B.K.; Essenburg, A.D.; Kieft, K.A.; Krause, B.R.; Staneld, R.L. Inhibitors of acyl-CoA:cholesterol acyltransferase. 1. Identification and structure-activity relationships of a novel series of fatty acid anilide hypocholesterolemic agents. J. Med. Chem., 1992, 35, 1609-1617.
49. Nagamitsu, T.; Sunazuka, T.; Obata, R.; Tomoda, H.; Tanaka, H.; Harigaya, Y.; Omura, S.; Smith, A.B. Total Synthesis of (+)- Pyripyropene A, a potent, orally bioavailable inhibitor of Acyl- CoA:cholesterol acyltransferase. J. Org. Chem., 1995, 60, 8126-8127.
50. Largis, E.E.; Wang, C.H.; DeVries, V.G.; Schaer, S.A. CL 277,082: a novel inhibitor of ACAT-catalyzed cholesterol esterification and cholesterol absorption. J. Lipid Res., 1989, 30, 681-690.
51. Ross, A.C.; Go, K.J.; Heider, J.G.; Rathblatt, G.H. Selective inhibition of acyl coenzyme A:cholesterol acyltransferase by compound SA-58-035. J. Biol. Chem. 1984, 259, 815-819.
52. Ashton, M.J.; Bridge, A.W.; Bush, R.C.; Dron, D.I.; Harris, N.V.; Jones, G.D.; Lythgoe, D.J.; Riddell, D.; Smith, C. RP 70676: A potent systematically available inhibitor of acyl-CoA:cholesterol Oacyl transferase (ACAT). Bioorg. Med. Chem. Lett., 1992, 2, 375-380.
53. Cadigan, K.M.; Heider, J.G.; Chang, T.Y. Isolation and characterization of chinese hamster ovary cell mutants deficient in acylcoenzyme A: cholesterol acyltransferase activity. J Biol. Chem., 1988, 263, 274-282.
54. Schmitz, G.; Robenek, H.; Beuck, M.; Krause, R.; Schurek, A.; Niemann R. Ca++ antagonists and ACAT inhibitors promote cholesterol efflux from macrophages by different mechanisms. Arteriosclerosis, 1988, 8, 46-56.
55. Bernard, D.W.; Rodriguez, A.; Rothblat, G.H.; Glick, J.M. Influence of high density lipoprotein on esterified cholesterol stores in macrophages and hepatoma cells. Arteriosclerosis, 1990, 10, 135-144.
56. Rodriguez, A.; Bachorik, P.S.; Wee, S.B. Novel effects of the acylcoenzyme A: cholesterol acyltransferase inhibitor 58-035 on foam cell development in primary human monocyte-derived macrophages. Arterioscler. Thromb. Vasc. Biol., 1999, 19, 2199-2206.
57. Bocan, T.M.; Mueller, S.B.; Uhlendorf, P.D.; Newton, R.S.; Krause, B.R. Comparison of CI-976, an ACAT inhibitor, and selected lipid-lowering agents for antiatherosclerotic activity in iliacfemoral and thoracic aortic lesions. A biochemical, morphological, and morphometric evaluation. Arterioscler. Thromb. Vasc. Biol., 1991, 11, 1830-1143.
58. Accad, M.; Smith, S.J.; Newland D.L.; Sanan, D.A.; King, L.E.; Linton, M.F.; Fazio, S. Massive xanthomatosis and altered composition of atherosclerotic lesions in hyperlipidemic mice lacking acyl CoA:cholesterol acyltransferase. J. Clin. Invest., 2000, 105, 711-719.
59. Yagyu, H.; Kitamine, T.; Osuga, J.; Tozawa, R.; Chen, Z.; Kaji, Y.; Oka, T. Absence of ACAT-1 attenuates atherosclerosis but causes dry eye and cutaneous xanthomatosis in mice with congenital hyperlipidemia. J. Biol. Chem., 2000, 275, 21324-21330.
60. Fazio, S.; Major, A.S.; Swift, L.L.; Gleaves L.A.; Accad, M.; Linton, M.F.; Farese, R.V. Increased atherosclerosis in LDL receptornull mice lacking ACAT1 in macrophages. J. Clin. Invest., 2001, 107, 163-171.
61. Kusunoki, J.; Hansoty, D.K.; Aragane, K.; Fallon, J.T.; Badimon, J.J.; Fisher, E.A. Acyl-CoA:cholesterol acyltransferase inhibition reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation, 2001, 103, 2604-2609.
62. Junquero, D.; Oms, P.; Carilla-Durand, E.; Autin, J.; Tarayre, J.; Degryse, A.; Patoiseau J. Pharmacological profile of F12511, (S)- 2',3',5'-trimethy- 4'-hydroxy-alpha- dodecylthioacetanilide, a powerful and systemic acylcoenzyme A:cholesterol acyltransferase inhibitor. Biochem. Pharmacol., 2001, 61, 97-108.
63. Warner, G.J.; Stoudt, G.; Bamberger, M.; Johnson, W.J.; Rothblat, G.H. Cell toxicity induced by inhibition of acyl coenzyme A:cholesterol acyltransferase and accumulation of unesterified cholesterol. J. Biol. Chem., 1995, 270, 5772-5778.
64. Feng, B.; Yao, P.M.; Li, Y.; Devlin, C.M.; Zhang, D.; Harding, H.P.; Sweeney, M. The endoplasmic reticulum is the site of cholesterol- induced cytotoxicity in macrophages. Nat. Cell. Biol., 2003, 5, 781-792.
65. Sahi, J.; Milad, M.A.; Zheng, X.; Rose, K.A.; Wang, H.; Stilgenbauer, L.; Gilbert, D. Avasimibe induces CYP3A4 and multiple drug resistance protein 1 gene expression through activation of the pregnane X receptor. J. Pharmacol. Exp. Ther., 2003, 306, 1027-1034.
66. Folkers, K.; Vadhanavikit, S.; Mortensen, S.A. Biochemical rational and myocardial tissue data on the effective therapy of cardiomyopathy with coenzyme Q10. Proc. Natl. Acad. Sci. USA, 1985, 82, 901-904
67. Mitchell, P. Possible molecular mechanisms of the protonmotive function of cytochrome systems. J. Theor. Biol., 1976, 62, 327-367.
68. Mitchell, P. Highlights in Ubiquinone Research, Taylor and Francis: London, 1990.
69. Lenaz, G.; Fato, R.; Castelluccio, C.; Battino, M.; Cavazzoni, M.; Rauchova, H.; Castelli, G.P. Biomedical and Clinical Aspects of Coenzyme Q 6, Elsevier: Amsterdam, 1991.
70. Linnane, W.A.; Kiosa, M.; Vitetta, L. Coenzyme Q10 - Its role as a prooxidant in the formation of superoxide anion/hydrogen peroxide and the regulation of the metabolome. Mitochondria, 2007, 7, S51-S61.
71. Bowry, V.W.; Mohr, D.; Cleary, J.; Stocker, R. Prevention of Tocopherol- mediated Peroxidation in Ubiquinol-10-free Human Low Density Lipoprotein. J. Biol. Chem., 1995, 270, 5756-5763.
72. Ghirlanda, G.; Oradei, A.; Manto, A.; Lippa, S.; Uccioli, L.; Caputo, S.; Greco, A.V.; Littarru, G.P. Evidence of Plasma CoQ10 - Lowering Effect by HMG-CoA Reductase Inhibitors: Adouble blind, placebo-controlled study. Clin. Pharmocol. J., 1993, 33, 226-229.
73. Ingold, K. U.; Bowry, V. W.; Stocker, R.; Walling, C. Autoxidation of lipids and antioxidation by alpha-tocopherol and ubiquinol in homogeneous solution and in aqueous dispersions of lipids: unrecognized consequences of lipid particle size as exemplified by oxidation of human low density lipoprotein. Proc. Natl. Acad. Sci. USA, 1993, 90, 45-49.
74. Langsjoen, P.; Willis, R.; Folkers, K. Treatment of essential hypertension with coenzyme Q10. Mol. Aspects Med., 1994, 15, S265-72.
75. Witting, P.K.; Pettersson, K.; Letters, J.; Stocker, R. The effect of α-tocopherol on the oxidative cleavage of β-carotene. Free. Radical. Biol. Med., 2000, 29, 105-114.
76. Langsjoen, H.; Langsjoen, P.; Willis, R.; Folkers, K. Usefulness of coenzyme Q10 in clinical cardiology: a long-term study. Mol. Aspects Med., 1994, 15, 165-175.
77. Munkhlom, H.; Hansen, H.H.; Rasmussen, K. Coenzyme Q 10 treatment in serious heart failure. BioFactors., 1999, 9, 285-289.
78. Watson, J.A.; Fang, M.; Lowenstein, J.M. Tricarballylate and hydroxycitrate: Substrate and inhibitor of ATP: citrate oxaloacetate lyase. Arch. Biochem. Biophys., 1969, 135, 209-217.
79. Cheema D.S.; Halperin, M.L.; Leznoff, C.C. Inhibition of enzymes which interact with citrate by (-) hydroxycitrate and 1,2,3,- tricarboxybenzene. Eur. J. Biochem., 1973, 38, 98-102.
80. Lowestein, J. M.; Brunengraber, H. Hydroxycitrate. Methods Enzymol., 1981, 72, 486-497.
81. Elshourbagy, N.A.; Near, J.C.; Kmetz, P.J.; Sathe, G.M.; Southan, C.; Strickler, J.E.; Gross, M.; Young, J.F.; Wells, T.N.; Groot, P.H. Rat ATP citrate-lyase. Molecular cloning and sequence analysis of a full-length cDNA and mRNA abundance as a function of diet, organ, and age. J. Biol. Chem., 1990, 265, 1430-1435.
82. Suzuki, F.; Tanioka H.; Takeda, Y. Studies on ATP citrate lyase of rat liver. J. Biochem., 1968, 63, 89-100.
83. Wonduck Kim and F. Robert Tabita. Both Subunits of ATP-Citrate Lyase from Chlorobium tepidum Contribute to Catalytic Activity. J. Bacteriol., 2006, 188, 6544-6552.
84. Giusto, N.M.; Pasquaré, S.J.; Salvador, G.A.; Castagnet, P.I.; Roque, M.E.; Ilincheta de Boschero, M.G. Lipid metabolism in vertebrate retinal rod outer segments. Prog. Lipid. Res., 2000, 39, 315-391.
85. Brunengraber, H.; Sabine, J.R.; Boutry, M.; and Lowenstein, J.M. 3- -Hydroxysterol synthesis by the liver. Arch. Biochem. Biophys., 1972, 150, 392-926.
86. Barth, C.; Hackensmidt, J.; Ullmann, H.; Decker, K. Inhibition of cholesterol synthesis by (-)-hydroxycitrate in perfused rat liver. Evidence for an extramitochondrial mevalonate synthesis from acetyl coenzyme A. FEBS Lett., 1972, 22, 343-346.
87. Lowenstein, J.M. Effect of (-)-hydroxycitrate on fatty acid synthesis by rat liver in vivo. J. Biol. Chem., 1971, 246, 629-632.
88. Hamilton, J.G.; Sullivan, A.C.; Kritchevsky, D. Hupolipidemic activity of (--)-hydroxycitrate. Lipids, 1977, 12, 1-9.
89. Berknout, T.A.; Havekes, L.M.; Pearce, N.J.; Groot, P.H. The effect of (-)-hydroxycitrate on the activity of the low-densitylipoprotein receptor and 3-hydroxy-3-methylglutaryl-CoA reductase levels in the human hepatoma cell line Hep G2. Biochem. J. 1990, 272, 181-186.
90. Pearce, N.J.; Yates, J.W.; Berkhout, T.A.; Jackson, B.; Tew, D.; Boyd, H.; Camilleri, P.; Sweeney, O.; Gribble, A.D.; Shaw, A.; Groot, P.H. The role of ATP citrate-lyase in the metabolic regulation of plasma lipids. Hypolipidaemic effects of SB-204990, a lactone prodrug of the potent ATP citrate-lyase inhibitor SB-201076. Biochem. J., 1998, 334, 113-119.
91. Gribble, A.D.; Dolle, R.E.; Shaw, A.; McNair, D.; Novelli, R.; Novelli, C.E.; Slingsby, B.P.; Shaw, V.P.; Tew, D.; Saxty, B.A.; Allen, M.; Groot, P.H.; Pearce, N.; Yates, J. ATP-citrate lyase as a target for hypolipidemic intervention. Design and synthesis of 2- substituted butanedioic acids as novel, potent inhibitors of the enzyme. J. Med. Chem. 1996, 39, 3569-3584.
92. Groot, P.H.E., Pearce, N.J.; Gribble, A.D. ATP-citrate lyase: A potential target for hypolipidemicintervention. Curr. Med. Chem. Immunol. Endocr. Metab. Agents, 2003, 3, 211-217.
93. Russel, J.C. Development of insulin resistance in the JCR:LA-cp rat: role of triacylglycerols and effects of MEDICA 16. Diabetes, 1998, 47, 770-778.
94. Asztalos, B.F.; Batista, M.; Horvath, K.V.; Cox, C.E.; Dallal, G.E.; Josh S. Morse, J.S.; Brown, G.B.; Schaefer, E.J. change in hdl concentration predicts progression in coronary artery stenosis. Arterioscler. Thromb. Vasc. Biol., 2003, 23, 847-852.
95. Picardo, M.; Massey, J.B.; Kuhn, D.E.; Gotto, A.M., Jr.; Gianturco, S.H.; Pownall, H.J. Partially reassembled high density lipoproteins. Effects on cholesterol flux, synthesis, and esterification in normal human skin fibroblasts. Arterioscler. Thromb. Vasc. Biol., 1986, 6, 434-441.
96. Ikonen, E. Mechanisms for cellular cholesterol transport: defects and human disease. Physiol. Rev., 2006, 86, 1237-1261.
97. Miller, G.J; Miller, N.E. Plasma-high-density-lipoprotein concentration and development of ischaemic heart-disease. Lancet, 1975, 4, 16-19.
98. Fielding, C.J.; Fielding, P.E. Molecular physiology of reverse cholesterol transport. J. Lipid Res., 1995, 36, 211-228.
99. Cohen, J.C; Grundy, S.M. Normal postprandial lipemia in men with low plasma HDL concentrations Arterioscler. Thromb. Vasc. Biol., 1992, 12, 972-975.
100. Groot, P.H; Scheek, L.M. Effects of fat ingestion on high density lipoprotein profiles in human sera. J. Lipid. Res., 1984, 25, 684-692.
101. Kashyap, M.L.; Barnhart, R.L.; Srivastava, L.S.; Perisutti, G.; Vink, P.; Allen, C.; Hogg, E.; Brady, D.; Glueck, C.J.; Jackson, R.L. Effects of dietary carbohydrate and fat on plasma lipoproteins and apolipoproteins C-II and C-III in healthy men. J. Lipid Res. 1982, 23, 877-886.
102. Tall, A.R.; Blum, C.B.; Forester, G.P.; Nelson, C.A. Changes in the distribution and composition of plasma high density lipoproteins after ingestion of fat. J. Biol. Chem., 1982, 257, 198-207.
103. DeBruin, T.W.; Brouwer, C.B.; Gimpel, J.A.; Erkelens, D.W. Postprandial decrease in HDL cholesterol and HDL apo A-I in normal subjects in relation to triglyceride metabolism. Am. J. Physiol. Endocrinol. Metab., 1991, 260, E492-E498.
104. Patsch, J.R.; Prasad, S.; Gotto, Jr. A.M.; Bengtsson-Olivecrona, G. Postprandial lipemia. A key for the conversion of high density lipoprotein2 into high density lipoprotein3 by hepatic lipase. J. Clin. Invest., 1984, 74, 2017-2023.
105. Navab, M; Hama, S.Y.; Hough, G.P.; Hedrick, C.C.; Sorenson, R.T.; La Du, B.N.; Kobashigawa, J.A.; Fonarow, G.C.; Berliner, J.A.; Laks, H.; Fogelman, A.M. High density associated enzymes: their role in vascular biology. Curr. Opin. Lipidol., 1998, 9, 449-456.
106. Lassel, T.S.; Guérin, M.; Auboiron, S.; Chapman, M.J.; Guy-Grand, B. Preferential cholesteryl ester acceptors among triglyceride- rich lipoproteins during alimentary lipemia in normolipidemic subjects. Arterioscler. Thromb. Vasc. Biol., 1998, 18, 65-74.
107. Lottenberga, S.A.; Lottenberga, A.M.P.; Nunesc, V.S.; McPhersond, R.; Quintão E.C.R. Plasma cholesteryl ester transfer protein concentration, high-density lipoprotein cholesterol esterification and transfer rates to lighter density lipoproteins in the fasting state and after a test meal are similar in Type II diabetics and normal controls. Atherosclerosis, 1996, 127, 81-90.
108. Castro, G.R.; Fielding, C.J. Effects of postprandial lipemia on plasma cholesterol metabolism. J. Clin. Invest. 1985, 75, 874-882.
109. Tall, A.; Sammett, D.; Granot, E. Mechanisms of enhanced cholesteryl ester transfer from high density lipoproteins to apolipoprotein B-containing lipoproteins during alimentary lipemia. J. Clin. Invest., 1986, 77, 1163-1172.
110. Tall, A.R.; Krumholz, S.; Olivecrona, T.; Deckelbaum, R.J. Plasma phospholipid transfer protein enhances transfer and exchange of phospholipids between very low density lipoproteins and high density lipoproteins during lipolysis. J. Lipid. Res., 1985, 26, 842-851.
111. Jauhiainen, M.; Metso, J.; Pahlman, R.; Blomqvist, S.; van Tol, A.; Ehnholm, C. Human plasma phospholipid transfer protein causes high density lipoprotein conversion. J. Biol. Chem. 1993, 268, 4032-4036.
112. Tu, A.Y.; Nishida, H.I.; Nishida, T. High density lipoprotein conversion mediated by human plasma phospholipid transfer protein. J. Biol. Chem., 1993, 268, 23098-23105.
113. Elokdah, H.; Chai, S.Y.; Ho, D.; Sulkowski, T. Design and synthesis of tricyclic derivatives as high density lipoprotein cholesterol enhancers. Bioorg. Med. Chem. Lett., 2001, 11, 339-342.
114. Lee, C.H.; Jeong, T.S.; Choi, Y.K.; Hyun, B.H.; Oh, G.T.; Kim, E.H.; Kim, J.-R.; Han, J.I.; Bok, S.H. Anti-atherogenic effect of citrus flavonoids, naringin and naringenin, associated with hepatic ACAT and aortic VCAM-1 and MCP-1 in high cholesterol-fed rabbits. Biochem. Biophys. Res. Commun., 2001, 284, 681-688.
115. Lee, S.; Lee, C.H.; Moon, S.S.; Kim, E.; Kim, C.T.; Kim, B.H.; Bok, S.H; Jeong, T.S. Naringenin derivatives as anti-atherogenic agents. Bioorg. Med. Chem. Lett., 2003, 13, 3901-3903.
116. Lee, S.; Lee, C.-H.; Oh, J.-H.; Kim, E. E.; Choi, Y.-K.; Kim, E.-H.; Lee, W.S.; Bok, S.-H.; Jeong, T.-S. Anti-atherogenic effects of 3,4- Dihydroxy hydrocinnamides. Bioorg. Med. Chem. Lett., 2003, 13, 2681-2682.
117. Weirzbicki, A.S. Imidazole derivatives as cholesterol-lowering agents. Int. J. Cardiol., 2003, 90, 141-145.
118. Seidell, J.C. Obesity, insulin resistance and diabetes - a worldwide epidemic. Br. J. Nutr., 2000, 83, S5-S8.
119. Howard, B.V. Insulin resistance and lipid metabolism. Am. J. Cardiol., 1999, 84, 28J-32J.
120. Wagner, A.M.; Perez, A.; Calvo, F.; Bonet, R.; Castellvi, A.; Ordonez, J. Apolipoprotein(B) identifies dyslipidemic phenotypes associated with cardiovascular risk in normocholesterolemic type 2 diabetic patients. Diabetes Care, 1999, 22, 812-817.
121. Duvillard, L.; Pont, F.; Florentin, E.; Galland-Jos, C.; Gambert, P.; Verges, B. Metabolic abnormalities of apolipoprotein B-containing lipoproteins in non-insulin-dependent diabetes: a stable isotope kinetic study. Eur. J. Clin. Invest., 2000, 30, 685-694.
122. Shelton, J.M.; Lee, M.-H.; Richardson, J.A.; Patel, S.B. Microsomal triglyceride transfer protein expression during mouse development. J. Lipid. Res., 2000, 41, 532-537.
123. Gordon, D.A.; Jamil, H. Progress towards understanding the role of microsomal triglyceride transfer protein in apolipoprotein-B lipoprotein assembly. Biochim. Biophys. Acta., 2000, 1486, 72-83.
124. Raabe, M.; Kim, E.; Veniant, M.; Nielsen, L.B.; Young, S.G. Using genetically engineered mice to understand apolipoprotein-B deficiency syndromes in humans. Proc. Assoc. Am. Physicians, 1998. 110, 521-530.
125. Wetterau, J.R.; Gregg, R.E.; Harrity, T.W.; Arbeeny, C.; Cap, M.; Connolly, F.; Chu, C.H.; George, R.J.; Gordon, D.A.; Jamil, H.; Jolibois, K.G.; Kunselman, L.K.; Lan, S.J.; Maccagnan, T.J.; Ricci, B.; Yan, M.; Young, D.; Chen, Y.; Fryszman, O.M.; Logan, J.V.; Musial, C.L.; Poss, M.A.; Robl, J.A.; Simpkins, L.M.; Slusarchyk, W.A.; Sulsky, R.; Taunk, P.; Magnin, D.R.; Tino, J.A.; Lawrence, R.M.; Dickson, J.K. Jr.; Biller, S.A. An MTP inhibitor that normalizes atherogenic lipoprotein levels in WHHL rabbits. Science, 1998, 282, 751-754.
126. Taghibiglou, C.; Carpentier, A.; VanIderstine, S.C.; Chen, B.; Rudy, D.; Aiton, A.; Lewis, G.F.; Adeli, K. Mechanisms of hepatic very low density lipoprotein overproduction in insulin resistance. Evidence for enhanced lipoprotein assembly, reduced intracellular ApoB degradation, and increased microsomal triglyceride transfer protein in a fructose-fed hamster model. J. Biol. Chem., 2000, 275, 8416-8425.
127. Hamilton, R.L.; Wong, J.S.; Cham, C.M.; Nielsen, L.B.; Young, S.G. Chylomicron-sized lipid particles are formed in the setting of apolipoprotein B deficiency. J. Lipid. Res., 1998, 39, 1543-1557.
128. Ginsberg, H.N. Diabetic dyslipidemia: basic mechanisms underlying the common hypertriglyceridemia and low HDL cholesterol levels. Diabetes, 1996, 45, S27-S30.
129. Hagan, D.L.; Kienzle, B.; Jamil, H.; Hariharan, N. Transcriptional regulation of human and hamster microsomal triglyceride transfer protein genes. Cell type-specific expression and response to metabolic regulators. J. Biol. Chem., 1994, 269, 28737-28744.
130. Reaven, G.M.; Greenfield, M.S. Diabetic hypertriglyceridemia: evidence for three clinical syndromes. Diabetes, 1981, 30, 66-75.
131. Lin, M.C.; Gordon, D.; Wetterau, J.R. Microsomal triglyceride transfer protein (MTP) regulation in HepG2 cells: insulin negatively regulates MTP gene expression. J. Lipid. Res., 1995, 36, 1073-1081.
132. Mathur, S.N.; Born, E.; Murthy, S.; Field, F.J. Microsomal triglyceride transfer protein in CaCo-2 cells: characterization and regulation. J. Lipid. Res., 1997, 38, 61-67.
133. Hussain, M.M.; Shi, J.; Dreizen, P. Microsomal triglyceride transfer protein and its role in apoB-lipoprotein assembly. J. Lipid. Res., 2003, 44, 22-32.
134. Hussain, M.M.; Iqbal, J.; Anwar, K.; Rava, P.; Dai, K. Microsomal triglyceride transfer protein: a multifunctional protein. Front. Biosci., 2003, 8, 500-506.
135. Wetterau, J.R.; Ailversmitt, D.B. Localization of intracellular triacylglycerol and cholesteryl ester transfer activity in rat tissues. Biochem. Biophys. Acta, 1986, 875, 610-617.
136. Jamil, H.; Chu, C.H.; Dickson, Jr. J.K. Evidence that microsomal triglyceride transfer protein is limiting in the production of apolipoprotein B-containing lipoproteins in hepatic cells. J. Lipid Res., 1998, 39, 1448-1454.
137. Magnin, D.R.; Biller, S.C.; Wetterau, J.; Robl, J.A.; Dickson, Jr. J.K.; Taunk, P.; Harrity, T.W.; Lawrence, R. M.; Sun, C.Q.; Wang, T.; Logan, J.; Fryszman, O.M.; Connolly, F.; Jolibois, K.; Kunselman, L. Microsomal triglyceride transfer protein inhibitors: discovery and synthesis of alkyl phosphonates as potent MTP inhibitors and cholesterol lowering agents. Bioorg. Med. Chem. Lett., 2003, 13, 1337-1340.
138. Shiomi, M.; Ito, T. MTP inhibitor decreases plasma cholesterol levels in LDL receptor-deficient WHHL rabbits by lowering the VLDL secretion. Eur. J. Pharmacol., 2001, 431, 127-131.
139. Barter, P.J.; Brewer, Jr. H.B.; Chapman, M.J.; Hennekens, C.H.; Rader, D.J.; Tall, A.R. Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis. Arterioscler. Thromb. Vasc. Biol., 2003, 23, 160-167.
140. Tall, A. R. Plasma cholesteryl ester transfer protein. J. Lipid. Res., 1993, 34, 1255-1274.
141. Grooth, J.G.; Kuivenhoven, J.A.; Stalenhoef, A.F.H.; Jacqueline de, G.; Zwinderman, A.H.; Posma, J.L.; Tol, A V.; Kastelein, J.P. Efficacy and safety of a novel cholesteryl ester transfer protein inhibitor, JTT-705, in humans: a randomized phase II dose-response study. Circulation, 2002, 105, 2159-2165.
142. Barter, P.J.; Hopkins, C. J.; Calvert, G. D. Transfers and exchanges of esterified cholesterol between plasma lipoproteins. Biochem. J., 1982, 208, 1-7.
143. Agellon, L.B.; Walsh, A.; Hayek, T.; Moulin P.; Jiang X.C.; Shelanski S.A.; Breslow J.L.; Tall, A.R. Reduced high density lipoprotein cholesterol in human cholesteryl ester transfer protein transgenic mice. J. Biol. Chem., 1991, 266, 10796-10801.
144. Jiang, X.C.; Walsh, A.; Breslow, J.L.; Tall, A.R.; Mar, J.; Lin, M. Down-regulation of mRNA for the low density lipoprotein receptor in transgenic mice containing the gene for human cholesteryl ester transfer protein. Mechanism to explain accumulation of lipoprotein B particles. J. Biol. Chem., 1993, 268, 27406-27412.
145. Marotti, K.R.; Castle, C.K.; Boyle, T.P.; Lin, A.H.; Murray, R.W.; Melchior, G.W. Severe atherosclerosis in transgenic mice expressing simian cholesteryl ester transfer protein. Nature, 1993, 364, 73-75.
146. Okamoto, H.; Yonemori, F.; Wakitani, K.; Minowa, T.; Maeda, K.; Shinkai, H.A Cholesteryl ester transfer protein inhibitor attenuates atherosclerosis in rabbits. Nature, 2000, 406, 203-207.
147. Bisgaier, C.L.; Essenburg, A.D.; Minton, L.L.; Homan, R.; Blankley, C.J.; White, A. Cholesteryl ester transfer protein inhibition by PD 140195. Lipids, 1994, 29, 811-818.
148. Durley, R.C.; Grapperhus, M.L.; Massa, M.A.; Mischke, D.A.; Parnas, B.L.; Fobian, Y.M.; Rath, N.P.; Honda, D.D.; Zeng, M.; Connolly, D.T.; Heuvelman, D.M.; Witherbee, B.J.; Glenn, K.C.; Krul, E.S.; Smith, M.E.; Sikorski, J.A. Discovery of chiral N,Ndisubstituted trifluoro-3-amino-2-propanols as potent inhibitors of cholesteryl ester transfer protein. J. Med. Chem., 2000, 43, 4575-4578.
149. Connolly, D.T.; Witherbee, B.J.; Melton, M.A.; Durley, R.C.; Grapperhaus, M.L.; McKinnis, B.R.; Vernier, W.F.; Babler, M.A.; Shieh, J.J.; Smith, M.E.; Sikorski, J.A. Stereospecific inhibition of CETP by chiral N,N-disubstituted trifluoro-3-amino-2-propanols. Biochemistry, 2000, 39, 13870-13879.
150. Ridker, P.M. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation, 2003, 107, 363-369.
151. Ross, R. Atherosclerosis-an inflammatory disease. N. Engl J. Med., 1999, 340, 115-126.
152. Blake, G.J.; Ridker P.M. Novel clinical markers of vascular wall inflammation. Circ. Res. 2001, 89, 763-771.
153. Bloomgarden, Z.T. Inflammation, atherosclerosis, and aspects of insulin action. Diabetes Care, 2005, 28, 2312-2319.
154. Ridker, P.M; Rifai, N.; Rose, L.; Buring, J.E.; Cook, N.R. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N. Engl. J. Med. 2002, 347, 1557-1565.
155. Torzewski, J.; Torzewski, M.; Bowyer, D. E.; Frohlich, M.; Koenig, W.; Waltenberger, J.; Fitzsimmons, C.; Hombach, V. Creactive protein frequently colocalizes with the terminal complement complex in the intima of early atherosclerotic lesions of human coronary arteries. Arterioscler. Thromb. Vasc. Biol., 1998, 18, 1386-1392.
156. Vasojima, K.; Schwab, C.; McGeer, E.G.; McGeer, P.L. Generation of C-reactive protein and complement components in atherosclerotic plaques. Am. J. Pathol., 2001, 158, 1039-1051.
157. Libby, P.; Ridker, P.M. Novel inflammatory markers of coronary risk: theory versus practice. Circulation, 1999, 100, 1148-1150.
158. Pasceri, V.; Willerson, J.T.; Yeh, E.T. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation, 2000, 102, 2165-2168.
159. Verma, S.; Wang, C. H.; Li, S.H.; Dumont, A.S.; Fedak, P.W.; Badiwala, M.V.; Dhillon, B.; Weisel, R.D.; Li, R.K.; Mickle, D.A.; Stewart, D.J. A self-fulfilling prophecy: C-reactive protein attenuates nitric oxide production and inhibits angiogenesis. Circulation, 2002, 106, 913-919.
160. Devaraj, S.; Xu, D.Y.; Jialal, I. C-reactive protein increases plasminogen activator inhibitor-1 expression and activity in human aortic endothelial cells: implications for the metabolic syndrome and atherothrombosis. Circulation, 2003, 107, 398-404.
161. Cleland, S.J.; Sattar, N.; Petrie, J.R.; Forouhi, N.G.; Elliott, H.L.; Connell, J.M. Endothelial dysfunction as a possible link between C-reactive protein levels and cardiovascular disease. Clin. Sci.(Lond), 2000, 98, 531-535.
162. Paul, A.; Ko, K. W.; Li, L.; Yechoor, V.; McCrory, M. A.; Szalai, A. J.; Chan, L. C-reactive protein accelerates the progression of atherosclerosis in apolipoprotein E-deficient mice. Circulation, 2004, 109, 647-655.
163. Lewis, K.E.; Kirk, E.A.; McDonald, T.O.; Wang, S.; Wight, T.N.; O'Brien, K.D.; Chait, A. Increase in serum amyloid a evoked by dietary cholesterol is associated with increased atherosclerosis in mice. Circulation, 2004, 110, 540-545.
164. Jessup, W.; Kritharides, L.; Srocker, R. Lipid oxidation in atherogenesis: an overview. Biochem. Soc.Trans., 2004, 32, 134-138.
165. Chisolm, G.M.; Steinberg, D. The oxidative modification hypothesis of atherogenesis: an overview. Free Radic. Biol. Med., 2000, 28, 1815-1826
166. Gelissen, I.C.; Brown, A.J.; Mander, E.L.; Kritharides, L.; Dean, R.T.; Jessup, W. Sterol efflux is impaired from macrophage foam cells selectively enriched with 7-ketocholesterol. J. Biol. Chem., 1996, 271, 17852-17860.
167. Tamai, O.; Matsuoka, H.; Itabe, H.; Wada, Y.; Kohno, K.; Tsutomu Imaizumi, T. Single LDL apheresis improves endotheliumdependent vasodilatation in hypercholesterolemic humans. Circulation, 1997, 95, 76-82.
168. Biorkhem, I.; Henriksson-Freyschuss, A.; Breuer, O.; Diczfalusy, U.; Berglund, L.; Henriksson, P. The antioxidant butylated hydroxytoluene protects against atherosclerosis. Arterioscler. Thromb. Vasc. Biol., 1991, 11, 15-22.
169. Unangst, P.C.; Connor, D.T.; Cetenko, W.A.; Sorenson, R.J.; Kostlan, C.R.; Sircar, J.C.; Wright, C.D.; Schrier, D.J.; Dyer, R.D. Synthesis and biological evaluation of 5-[[3,5-bis(1,1- dimethylethyl)- 4-hydroxyphenyl]methylene]oxazoles, -thiazoles, and -imidazoles: novel dual 5-lipoxygenase and cyclooxygenase inhibitors with antiinflammatory activity. J. Med. Chem., 1994, 37, 322-328.
170. Jeong, T.S.; Kim, K.S.; Kim, J.R.; Cho, K.H.; Lee, S.; Lee, W.S. Novel 3,5-diaryl pyrazolines and pyrazole as low-density lipoprotein (LDL) oxidation inhibitor. Bioorg. Med. Chem. Lett., 2004, 14, 2719-2723.
171. Lohray, B.B.; Lohray, V.B.; Bajji, A.C.; Kalchar, S.; Poondra, R.R.; Padakanti, S.; Chakrabarti, R.; Vikramadithyan, R.K.; Misra, P.; Juluri, S.; Mamidi, N.V.; Rajagopalan, R. (-)3-[4-[2- (Phenoxazin-10-yl)ethoxy]phenyl]-2-ethoxypropanoic acid [(-)DRF 2725]: a dual PPAR agonist with potent antihyperglycemic and lipid modulating activity. J. Med. Chem., 2001, 44, 2675-268.
172. Madhavan, G.R.; Balraju, V.; Mallesham, B.; Chkrabarti, R.; Lohray, V.B. Novel coumarin derivatives of heterocyclic compounds as lipid-lowering agents. Bioorg. Med. Chem. Lett., 2003, 13, 2547-2551.
173. Chrysselis, M.C.; Rekka, E.A.; Kourounakis, P.N. Hypocholesterolemic and hypolipidemic activity of some novel morpholine derivatives with antioxidant activity. J. Med. Chem., 2000, 43, 609-612.
174. Vaughan, M.; Berger, J.E.; Steinberg, D. Hormone-sensitive lipase and monoglyceride lipase activities in adipose tissue. J. Biol. Chem., 1964, 239, 401-409.
175. Tsai, S.C.; Belfrage, P.; Vaughan, M. Activation of hormonesensitive lipase in extracts of adipose tissue. J. Lipid Res., 1970, 11, 466-472.
176. Stralfors, P.; Belfrage, P. Phosphorylation of hormone-sensitive lipase by cyclic AMP-dependent protein kinase. J. Biol. Chem., 1983, 258, 15146-15152.
177. Belfrage, P.; Fredrikson, G.; Olsson, H. Regulation of adipose tissue lipolysis through reversible phosphorylation of hormonesensitive lipase. Adv. Cyclic Nucleotide Protein Phosphorylation Res., 1984, 17, 351-359.
178. Haagsman, H.P.; de Haas, C.G.; Geelen, M.J. Regulation of triacylglycerol synthesis in the liver. Modulation of diacylglycerol acyltransferase activity in vitro. J. Biol. Chem., 1982, 257, 10593-10598.
179. Rodriguez, M.A.; Dias, C.; Lau, T.E. Reversible ATP-dependent inactivation of adipose diacylglycerol acyltransferase. Lipids, 1992, 27, 577-581.
180. Brindley, D.N. The fate of oil and oil-dispersant mixtures in freshwater ponds. Lipid Res., 1984, 23, 115-133.
181. Gomez-Munoz, A.; Hamza, E.H.; Brindley, D.N. Effects of sphingosine, albumin and unsaturated fatty acids on the activation and translocation of phosphatidate phosphohydrolases in rat hepatocytes Biophy. Acta., 1992, 1127, 49-56.
182. Mayorek, N.; Grinstein, I.; Bar-Tana, J. Triacylglycerol synthesis in cultured rat hepatocytes. The rate-limiting role of diacylglycerol acyltransferase. Eur. J. Biochem., 1989, 182, 395-400.
183. Stals, H.K.; Top, W.; Declercq, P.E. Regulation of triacylglycerol synthesis in permeabilized rat hepatocytes. Role of fatty acid concentration and diacylglycerol acyltransferase. FEBS Lett., 1994, 343, 99-102.
184. Mayorek, N.; Bar-Tana, J. Lipid synthesis in permeabilized cultured rat hepatocytes. J. Bio. Chem., 1989, 264, 4450-4455.
185. Coleman, R.A.; Bell, R.M. The Enzymes, Academic Press: New York, 1983.
186. Andersson, M.; Wettesten, M.; Borén, J.; Magnusson, A.; Sjöberg, A.; Rustaeus, S.; Olofsson, S.O. Purification of diacylglycerol: acyltransferase from rat liver to near homogeneity. J. Lipid Res., 1994, 35, 535-545.
187. Haagsman, H.P.; De Haas, C.G.; Geelen, M.J.; van Golde, L.M. Regulation of triacylglycerol synthesis in the liver: a decrease in diacylglycerol acyltransferase activity after treatment of isolated rat hepatocytes with glucagon. Biochim. Biophy. Acta, 1981, 664, 74-81.
188. Baldo, A.; Sniderman, A.D.; Cianflone, K. Increase in intracellular TG synthesis induced by gemfibrozil. Metabo: Clin. Exp., 1994, 43, 257-262.
189. Baldo, A.; Sniderman, A.D.; St Luce, S.; Zhang, X.J.; Cianflone, K. Signal transduction pathway of acylation stimulating protein: involvement of protein kinase C. J. Lipid Res., 1995, 36, 1415-1426.
190. Cianflone, K.; Vu, H.; Walsh, M.; Baldo, A.; Sniderman, A. metabolic response of acylation stimulating protein to an oral fat load. J. Lipid Res., 1989, 30, 1727-1733.
191. Baldo, A.; Sniderman, A.D.; St-Luce, S.; Avramoglu, R.K.; Maslowska, M.; Hoang, B.; Monge, J.C.; Bell, A.; Mulay, S.; Cianflone, K. The adipsin-acylation stimulating protein system and regulation of intracellular triglyceride synthesis. J. Clin. Invest., 1993, 92, 1543-1547.
192. Cianflone, K.; Roncari, D.A.; Maslowska, M.; Baldo, A.; Forden, J.; Sniderman, A.D. Adipsin/acylation stimulating protein system in human adipocytes: regulation of triacylglycerol synthesis. Biochemistry, 1994, 33, 9489-9495.
193. Germinario, R.; Sniderman, A.D.; Manuel, S. Coordinate regulation of triacylglycerol synthesis and glucose transport by acylationstimulating protein. Metab. Clin. Exp., 1993, 42, 574-580.
194. Yasruel, Z.; Cianflone, K.; Sniderman, A.D.; Rosenbloom, M.; Walsh, M.; Rodriguez, M.A. Effect of acylation stimulating protein on the triacylglycerol synthetic pathway of human adipose tissue. Lipids, 1991, 26, 495-499.
195. Smith, S.J.; Cases, S.; Jensen, D.R.; Chen, H.C.; Sande, E.; Tow, B.; Sanan, D.A.; Raber, J.; Eckel, R.H.; Farese, R.V. Jr. Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking DGAT. Nat. Genet., 2000, 25, 87-90.
196. Ludwig, E.H.; Mahley, R.W.; Palaoglu, E.; Ozbayrakçi, S.; Balestra, M.E.; Borecki, I.B.; Innerarity, T.L.; Farese, R.V. Jr. DGAT1 promoter polymorphism associated with alterations in body mass index, high density lipoprotein levels and blood pressure in Turkish women. Clin. Genet., 2002, 62, 68-73.
197. Trzaskos, J.M., Bowen W.D., Shafiee, A.; Fischer, R. T.; Gaylor, J.L. Cytochrome P450-dependent oxidation of lanosterol in cholesterol biosynthesis: microsomal electron transport and C-32 demethylation. J. Biol. Chem., 1984, 10, 13402-13412
198. Frye, L.L.; Cusack, K.P.; Leonard, D.A. 32-Methyl-32- oxylanosterols: dual-action inhibitors of cholesterol biosynthesis. J. Med. Chem., 1993, 36, 410-416.
199. Taylor, F.R.; Saucier, S.E.; Shown, E.P.; Parish, E.J.; Kandutsch, A.A. Correlation between oxysterol binding to a cytosolic binding protein and potency in the repression of hydroxymethylglutaryl coenzyme A reductase. J. Biol. Chem., 1984, 259, 12382-12387.
200. Chen, H.W. Increase of latent HMG-CoA reductase activity with increasing density of cell cultures. J. Cell. Physiol., 1983, 117, 123-127.
201. Gibbons, G.F.; Pullinger, C.R.; Chen, H.W.; Cavenee, W.K.; Kandutsch, A.A. Regulation of cholesterol biosynthesis in cultured cells by probable natural precursor sterols. J. Biol. Chem., 1980, 255, 395-400.
202. Kandutsch, A.A.; Chen, H.W.; Heiniger, H.J. Biological activity of some oxygenated sterols. Science, 1978, 201, 498-501.
203. Burton, P.M.; Swinney, D.C.; Heller, R.; Dunlap, B.; Chiou, M.; Malonzo, E.; Haller, J.; Walker, K.A.; Salari, A.; Murakami, S. Azalanstat (RS-21607), a lanosterol 14α-demethylase inhibitor with cholesterol-lowering activity. Biochem. Pharmacol., 1995, 50, 529-544.
204. Chhabria, M.T. Recent developments in the treatment of atherosclerosis. J. Enzyme Inhib. Med. Chem., 2006, 21, 1-15.
205. Tuck, S.F.; Robinsaon, C.H.; Silverton, J.V. Assessment of the active-site requirements of lanosterol 14.alpha.-demethylase: evaluation of novel substrate analogs as competitive inhibitors. J. Org. Chem., 1991, 56, 1260-1266.
206. Gaylor, J.L.; Johnson, P.R.; Ko, S.S.; Magolda, R.L.; Stam, S.H.; Trzaskos, J.M. US 5041432, 1991; (1989) Chem. Abstr., 110, 115192.
207. Mayer, R.J.; Adams, J.L.; Bossard, M.J.; Berkhout, T.A. Effects of a novel lanosterol 14 alpha-demethylase inhibitor on the regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in Hep G2 cells. J. Biol. Chem., 1991, 25, 20070-20078.
208. Kempen, H.J.M., Glatz, J.E.C.; Gevers Leuven, J.A.; van der Voort, H.A.; Katan, M.B. Serum lathosterol concentration is an indicator of whole-body cholesterol synthesis in humans. J. Lipid Res., 1988, 29, 1149-1155.
209. Fischer, R.T., Stam, S.H.; Johnson, P.R.; KO, S.S.; Magolda, R.L.; Gaylor, J.L.; Trzaskos, J.M. Mechanistic studies of lanosterol 14amethyl demethylase: substraterequirements for the component reactions catalyzed by a single cytochrome P-450 isozyme. J. Lipid Res., 1989, 30, 1621-1631.
210. Carazo, A.; Alejandre, M.J.; Louktibi, A.; Linares, A. The role of ATP citrate-lyase in the metabolic regulation of plasma lipids. Biochem. J., 1998, 334, 113-119.
211. Yang, S.S.; Chiang, Y.C. P.; Heck, J.V.; Chang, M.N. US 4983597, 1991; 1992 Chem. Abstr., 116, 20923.
212. Garrity, G.M.; Henses, O.D.; Glacobbe, R.A.; Joshua, H.; Greenspan, M.D.; Milligan, J.A.; Onishi, J.O.; Diez Matas, M.T.; Rozdilsky, W.; Del Val, S.M.; Martin, I.; Liesch, J.M. EP411703A1, 1991; 1991 Chem. Abstr., 115, 181508.
213. Harrity, T. W.; George, R. J.; Ciosek, C. P., Jr.; Biller, S. A.; Chen, Y.; Dickson, J. K., Jr.; Fryszman, O. M.; Jolibois, K. J.; Kunselman, L. K.; Lawrence, R. M.; Logan, J. V. H.; Magnin, D. R.; Rich, L. C.; Slusarchyk, D. A.; Sulsky, R. B.; Gregg, R. E. In XII International Symposium on Drugs Affecting Lipid Metabolism, 1995, vol. 54.
214. Sharma, A.; Slugg, P.H.; Hammett, J.L.; Jusko, W.J. Clinical pharmacokinetics and pharmacodynamics of a new squalene synthase inhibitor, BMS-188494, in healthy volunteers. J. Clin. Pharmacol., 1998, 38, 1116-1121.
215. Amin, D.; Rutledge, R. Z.; Needle, S. N.; Galczenski, H.F.; Neuenschwander, K.; Scotese, A.C.; Maguire, M.P.; Bush, R.C.; Hele, D.J.; Bilder, G.E.; Perrone, M.H. RPR 107393, a potent squalene synthase inhibitor and orally effective cholesterollowering agent: comparison with inhibitors of HMG-CoA reductase. J. Pharmacol. Exp. Ther., 1997, 281, 746-752.
216. Hiyoshi, H.; Yanagimachi, M.; Ito, M.; Ohtsuka, I.; Yoshida, I.; Saeki, T.; Tanaka, H. Effect of ER-27856, a novel squalene synthase inhibitor, on plasma cholesterol in rhesus monkeys: comparison with 3-hydroxy-3-methylglutaryl-coa reductase inhibitors. J. Lipid Res., 2000, 41, 1136-1144.
217. Hiyoshi, H.; Yanagimachi, M.; Ito, M.; Yasuda, N.; Okada, T.; Ikuta, H.; Shinmyo, D.; Tanaka, K.; Kurusu, N.; Yoshida, I.; Abe, S.; Saeki, T.; Tanaka, H. Squalene synthase inhibitors suppress triglyceride biosynthesis through the farnesol pathway in rat hepatocytes. J. Lipid Res., 2003, 44, 128-135.
218. Ugawa, T.; Kakuta, H.; Moritani, H.; Matsuda, K.; Ishihara, T.; Yamaguchi, M.; Naganuma, S.; Iizumi, Y.; Shikama, H. YM- 53601, a novel squalene synthase inhibitor, reduces plasma cholesterol and triglyceride levels in several animal species. Br. J. Pharmacol., 2000, 131, 63-70.
219. Summons, R.E.; Bradley, A.S.; Jahnke, L.L.; Waldbauer, J.R. Steroids, triterpenoids and molecular oxygen. Philos. Trans. R. Soc. Lond. B. Biol. Sci., 2006, 361, 951-968.
220. Shibata, N.; Jishage, K.-I.; Arita, M.; Watanabe, M.; Kawase, Y.; Nishikawa, K.; Natori, Y.; Inoue, H.; Shimano, H.; Yamada, N.; Tsujimoto, M.; Arai, H. Regulation of hepatic cholesterol synthesis by a novel protein (SPF) that accelerates cholesterol biosynthesis. FASEB J., 2006, 20, 2642-2644.
221. Cory, E.J.; Russey, W.E.; Ortiz de Montellano, P.R. 2,3- oxidosqualene, an intermediate in the biological synthesis of sterols from squalene. J. Am. Chem. Soc., 1966, 88, 4750-4751.
222. Van Tamelen, E.E.; Willett, J.D.; Clayton, R.B.; Lord, K.E. Enzymic conversion of squalene 2,3-oxide to lanosterol and cholesterol. J. Am. Chem. Soc., 1966, 88, 4752-4754.
223. Yamamoto, S.; Bloch, K. Studies on squalene epoxidase of rat liver. J. Biol. Chem., 1970, 245, 1670-1674.
224. Ono, T.; Bloch, K. Solubilization and partial characterization of rat liver squalene epoxidase. J. Biol. Chem., 1975, 250, 1571-1579.
225. Tai, H.H.; Bloch, K. Squalene epoxidase of rat liver. J. Biol. Chem., 1972, 247, 3767-3773.
226. Ferguson, J.B.; Bloch, K. Purification and properties of a soluble protein activator of rat liver squalene epoxidase. J. Biol. Chem., 1977, 252, 5381-5385.
227. Srikantaiah, M.V.; Hansbury, E.; Loughran, E.D.; Scallen, T.J. Purification and properties of sterol carrier protein1. J. Biol. Chem., 1976, 251, 5496-5504.
228. Shibata, N.; Arita, M.; Misaki, Y.; Dohmae, N.; Takio, K.; Ono, T.; Inoue, K.; Arai, H. Supernatant protein factor, which stimulates the conversion of squalene to lanosterol, is a cytosolic squalene transfer protein and enhances cholesterol biosynthesis. Proc. Natl. Acad. Sci. USA, 2001, 98, 2244-2249.
229. Astruc, M.; Tabacik, C.; Descomps, B.; de Paulet, A.C.; Squalene epoxidase and oxidosqualene lanosterol-cyclase activities in cholesterogenic and non-cholesterogenic tissues. Biochim. Biophys. Acta, 1977, 487, 204-211.
230. Nakamura, Y.; Sakakibara, J.; Izumi, T.; Shibata, A.; Ono, T. Transcriptional regulation of squalene epoxidase by sterols and inhibitors in HeLa cells. J. Biol. Chem., 1996, 271, 8053-8056.
231. Chugh, A.; Ray, A.; Gupta, J.B. Squalene epoxidase as hypocholesterolemic drug target revisited. Prog. Lipid Res., 2003, 42, 37-50.
232. Horie, M.; Tsuchiya, Y.; Hayashi, M.; Iida, Y.; Iwasawa, Y.; Nagata, Y.; Sawasaki, Y.; Fukuzumi, H.; Kitani, K.; Kamei, T. NB- 598: a potent competitive inhibitor of squalene epoxidase. J. Biol. Chem., 1990, 265, 18075-1808.
233. Horie, M.; Sawasaki, Y.; Fukuzumi, H.; Watanabe, K.; Iizuka, Y.; Tsuchiya, Y.; Kamei, T. Hypolipidemic effects of NB-598 in dogs. Atherosclerosis, 1991, 88, 183-192.
234. Jarvi, E.T.; Edwards, M.L.; McCarthy, J.R. US 5011859, 1991. Chem. Abstr., 1991, 115, 136448.
235. Van Sickle, W.A.; Angelastro, M.R.; Wilson, P.; Cooper, J.R.; Marquart, A.; Flanagan, M.A. Inhibition of cholesterol synthesis by cyclopropylamine derivatives of squalene in human hepatoblastoma cells in culture. Lipids, 1992, 27, 157-160.
236. Abe, I.; Seki, T.; Umehara, K.; Miyase, T.; Noguchi, H.; Sakakibara, J.; Ono, T. Green tea polyphenols: novel and potent inhibitors of squalene epoxidase. Biochem. Biophys. Res. Commun., 2000, 268, 767-771.
237. Chen, L.; Lee, M.J.; Li, H.; Yang, C.S. Absorption, distribution, elimination of tea polyphenols in rats. Drug. Metab. Dispos., 1997, 25, 1045-1050.
238. Abe, I.; Seki, T.; Noguchi, H.; Kashiwada, Y. Galloyl esters from rhubarb are potent inhibitors of squalene epoxidase, a key enzyme in cholesterol biosynthesis. Planta. Med., 2000, 66, 753-756.
239. Fremont, L. Biological effects of resveratrol. Life. Sci., 2000, 66, 663-673.
240. Laden, B.P.; Porter, T.D. Resveratrol inhibits human squalene monooxygenase. Nutrition Res., 2001, 21, 747-753.
241. Gupta, N.; Porter, T.D. Garlic and garlic-derived compounds inhibit human squalene monooxygenase. J. Nutr., 2001, 131, 1662-1667.
242. Blumberg, B.; Evans, R. M. Orphan nuclear receptors - New ligands and new possibilities. Genes, 1998, 12, 3149-3155.
243. Stach, D.; Zheng, Y.F.; Perez, A.L.; Oehlschlager, A.C. Synthesis and inhibition studies of sulfur-substituted squalene oxide analogues as mechanism-based inhibitors of 2,3-oxidosqualenelanosterol cyclase. J. Med. Chem., 1997, 40, 201-209.
244. Wannamaker, M.W.; Van Sickle, W.A.; Moore, W.R. US 5084461, 1992. Chem. Abstr., 1993, 118, 191562.
245. Taton, M.; Benveniste, P.; Rahier, A. Inhibition of 2,3- oxidosqualene cyclases. Biochemistry, 1992, 31, 7892-7898.
246. Morland, O.H.; Aebi, J.D.; Dehmlow, H.; Ji, Y.H.; Gains, N.; Lengsfeld, H.; Himber, J. Ro 48-8.071, 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.
247. Kliewer, S.A.; Lehmann, J.M.; Willson, T.M. Orphan nuclear receptors: shifting endocrinology into reverse. Science, 1999, 284, 757-760.
248. Mangelsdorf, D.J.; Evans, R.M. The RXR heterodimers and orphan receptors. Cell, 1995, 83, 841-850.
249. Eloranta, J.J.; Kullak-Ublick, G.A. Coordinate transcriptional regulation of bile acid homeostasis and drug metabolism. Arch. Biochem. Biophys., 2005, 433, 397-412.
250. Pellicciari, R.; Costantino, G.; Fiorucci, S. Farnesoid X receptor: from structure to potential clinical applications. J. Med. Chem., 2005, 48, 5383-5403.
251. Laffitte, B.A.; Kast, H.R.; Nguyen, C.M.; Zavacki, A.M.; Moore, D.D.; Edwards, P.A. Identification of the DNA binding specificity and potential target genes for the farnesoid X-activated receptor. J. Biol. Chem., 2000, 275, 10638-10647.
252. Parks, D.J.; Blanchard, S.G.; Bledsoe R.K.; Chandra, G.; Consler, T.G.; Kliewer, S.A.; Stimmel, J.B.; Willson, T.M.; Zavacki, A.M.; Moore, D.D.; Lehmann, J.M. Bile acids: natural ligands for an orphan nuclear receptor. Science, 1999, 284 1365-1368.
253. Fujino, T.; Une, M.; Imanaka, T.; Inoue, K.; Nishimaki-Mogami, T. Structure-activity relationship of bile acids and bile acid analogs in regard to FXR activation. J. Lipid Res., 2004, 45, 132-138.
254. Nishimaki-Mogami, T.; Une, M.; Fujino, T.; Sato, Y.; Tamehiro, N.; Kawahara, Y.; Shudo, K.; Inoue, K. Identification of intermediates in the bile acid synthetic pathway as ligands for the farnesoid X receptor. J. Lipid. Res., 2004, 45, 1538-1545.
255. Davis, R.A.; Miyake, J.H.; Hui, T.Y.; Spann, N.J. Regulation of cholesterol-7alpha-hydroxylase: BAREly missing a SHP. J. Lipid. Res., 2002, 43, 533-543.
256. Edwards, P.A.; Kast, H.R.; Anisfeld, A.M. BAREing it all: the adoption of LXR and FXR and their roles in lipid homeostasis J. Lipid Res., 2002, 43, 2-12.
257. Bledsoe, R.K.; Montana, V.G.; Stanley, T.B.; Delves, C.J.; Apolito, C.J.; McKee, D.D.; Consler, T.G.; Parks, D.J.; Stewart, E.L.; Willson, T.M.; Lambert, M.H.; Moore, J.T.; Pearce, K.H.; Xu, H.E. Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition. Cell, 2002, 110, 93-105.
258. Brzozowski, A.M.; Pike, A.C.; Dauter, Z.; Hubbard, R.E.; Bonn, T.; Engstrom, O.; Ohman, L.; Greene, G.L.; Gustafsson, J.A.; Carlquist, M. Molecular basis of agonism and antagonism in the oestrogen receptor. Nature, 1997, 389, 753-758.
259. Nettles, K.; Greene, G. Nuclear Receptor Ligands and Cofactor RecruitmentIs There a Coactivator "On Deck"?. Mol. Cell, 2003, 11, 850-851
260. Downes, M.; Verdecia, M.A.; Roecker, A.J.; Hughes, R.; Hogenesch, J.B.; Kast-Woelbern, H.R.; Bowman, M.E.; Ferrer, J.L.; Anisfeld, A.M.; Edwards, P.A.; Rosenfeld, J.M.; Alvarez, J.G.; Noel, J.P.; Nicolaou, K.C.; Evans, R.M. A chemical, genetic, and structural analysis of the nuclear bile acid receptor FXR. Mol. Cell, 2003, 11, 1079-1092.
261. Mi, L.Z.; Devarakonda, S.; Harp, J.M.; Han, Q.; Pellicciari, R.; Willson, T.M.; Khorasanizadeh, S.; Rastinejad, F. Structural basis for bile acid binding and activation of the nuclear receptor FXR. Mol. Cell, 2003, 11, 1093-1100.
262. Glass, C.K.; Rose, D.W.; Rosenfeld, M.G. Nuclear receptor coactivators. Curr. Opin. Cell. Biol., 1997, 9, 222-232.
263. Hoshita, T.; Nagayoshi, S.; Kazuno, T. Stero-bile acids and bile sterols. Liv. Studies on the bile of carp. J. Biochem., 1963, 54, 369-374.
264. Amos, B.; Anderson, I.G.; Haslewood, G.A.; Tokes, L. Bile salts of the lungfishes Lepidosiren, Neoceratodus and Protopterus and those of the coelacanth Latimeria chalumnae Smith. J. Biochem., 1977, 161, 201-204.
265. Une, M.; Matsumoto, N.; Kihira, K.; Yasuhara, M.; Kuramoto, T.; Hoshita, T. Bile salts of frogs: a new higher bile acid, 3 alpha, 7 alpha, 12 alpha, 26-tetrahydroxy-5 beta-cholestanoic acid from the bile Rana plancyi. J. Lipid Res., 1980, 21, 269-276.
266. Goodwin, B.; Jones, S.A.; Price, R.R.; Watson, M.A.; McKee, D.D.; Moore, L.B.; Galardi, C.; Wilson, J.G.; Lewis, M.C.; Roth, M.E.; Maloney, P.R.; Willson, T.M.; Kliewer, S.A. A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis. Mol. Cell., 2000, 6, 517-526.
267. Claudel, T.; Staels, B.; Kuipers, F. The Farnesoid X receptor: a molecular link between bile acid and lipid and glucose metabolism. Arterioscler. Thromb. Vasc Biol., 2005, 25, 2020-2030.
268. Lee, F.Y.; Lee, H.; Hubbert, M.L.; Edwards, P.A.; Zhang, Y. FXR, a multipurpose nuclear receptor. Trends Biochem. Sci., 2006, 31, 572-580.
269. Urizar, N.L.; Liverman, A.B.; Dodds, D.T.; Silva, F.V.; Ordentlich, P.; Yan, Y.; Gonzalez, F.J.; Heyman, R.A.; Mangelsdorf, D.J.; Moore, D.D. A natural product that lowers cholesterol as an antagonist ligand for FXR. Science, 2002, 296, 1703-1706.
270. Horton, J.D.; Goldstein, J.L.; Brown, M.S. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J. Clin. Invest., 2002, 109, 1125-1131.
271. Shimano, H. Sterol regulatory element-binding protein family as global regulators of lipid synthetic genes in energy metabolism. Vitam Horm., 2002, 65, 167-194.
272. Shimano, H. Sterol regulatory element-binding protein-1 as a dominant transcription factor for gene regulation of lipogenic enzymes in the liver. Trends Cardiov. Med., 2000, 10, 275-278.
273. Grand-Perret, T.; Bouillot, A.; Perrot, A. SCAP ligands are potent new lipid-lowering drugs. Nat. Med., 2001, 7, 1332-1338.
274. Rader, D.J. A new feature on the cholesterol-lowering landscape. Nat. Med., 2001, 7, 1282-1284.
275. Wernette-Hammond, M.E.; Lauer, S.J.; Corsini, A.; Walker, D.; Taylor, J.M.; Rall, S.C. Glycosylation of human apolipoprotein E. The carbohydrate attachment site is threonine 194. J. Biol Chem., 1989, 264, 9094-9101.
276. Mahley, R.W. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science, 1988, 240, 622-630.
277. Rall, S.C. Jr.; Mahley, R.W. The role of apolipoprotein E genetic variants in lipoprotein disorders. J. Intern. Med., 1992, 231, 653-659.
278. Rall, S.C. Jr.; Weisgraber, K.H.; Mahley, R.W. Human apoprotein E heterogeneity. Cysteine-arginine interchanges in the amino acid sequence of the apo E isoforms. J. Biol. Chem., 1981, 256, 9077-9083.
279. Wiebe, C.; Holzem1, G.; Wielckens, K.; Klingler, K.R. Apolipoprotein E polymorphism: Automated determination of apolipoprotein E2, E3, and E4 isoforms. Lipids, 2000, 35, 99-104.
280. Herz, J.U.; Rogne, H.S.; Gausepohl, M.H.; K.K. Surface location and high affinity for calcium of a 500-kd liver membrane protein closely related to the LDL-receptor suggest a physiological role as lipoprotein receptor. EMBO. J., 1988, 7, 4119-4127.
281. Takahashi, S.Y.; Kawarabayasi, T.; Sakai, N.J.; Yamamoto, T. Rabbit very low density lipoprotein receptor: A low density lipoprotein receptor-like protein with distinct ligand speciflcity. Proc. Natl. Acad. Sci. USA, 1992, 89, 9252-9256.
282. Willnow, T.E.; Goldstein, J.L.; Orth, K.; Brown, M.S.; Herz, J. Low density lipoprotein receptor-related otein and gp330 bind similar ligands, including plasminogen activator-inhibitor complexes and actoferrin, an inhibitor of chylomicron remnant clearance. J. Biol. Chem., 1992, 267, 26172-26180.
283. Shore, V.G., B. Shore, B. Heterogeneity of human plasma very low density lipoproteins. Separation of species differing in protein components. Biochemistry, 1973, 12, 502-507.
284. Hui, D.Y., Harmony, J.A.; Innerarity, T.L.; Mahley R.W. Immunoregulatory plasma lipoproteins. Role of apolipoprotein E and apolipoprotein B. J. Biol. Chem., 1980, 255, 11775-11781.
285. LeBlanc, A.C., Poduslo, J.F. Regulation of apolipoprotein E gene expression after injury of the rat sciatic nerve. J. Neurosci. Res., 1990, 25, 162-171.
286. Silvia, S.-F.; Herminia, G.-N.; Freeman, L.; Wagner, E.; Nong, Z. Hepatic Lipase, Lipoprotein Metabolism, and Atherogenesis. Arteriosclerosis. Thromb. Vas. Biol., 2004, 24, 1750-1754.
287. Santamarina-Fojo, S.; Haudenschild, C. Role of hepatic and lipoprotein lipase in lipoproten metabolism and atherosclerosis: studies in transgenic and knockout animal models and somatic gene transfers. Int. J. Tissue. React., 2000, 22, 39-47.
288. Zhu, Z.; Bellosta, S.; Langer, C.; Bernini, F.; Pitas, R.E.; Mahley, R.W.; Assmann, G.; von Eckardstein, A. Low-dose expression of a human apolipoprotein E transgene in macrophages restores cholesterol efflux capacity of apolipoprotein E-deficient mouse plasma. Proc. Natl. Acad. Sci. USA, 1998, 95, 7585-7590.
289. Cullen, P.; Cignarella, A.; Brennhausen, B.; Mohr, S.; Assmann, G.; von Eckardstein, A. Phenotype-dependent differences in apolipoprotein E metabolism and in cholesterol homeostasis in human monocyte-derived macrophages. J. Clin. Invest., 1998, 101, 1670-1677.
290. Wilson, P.W.; Schaefer, E.J.; Larson, M.G.; Ordovas, J.M. Apolipoprotein E alleles and risk of coronary disease. A meta-analysis. Arterioscler. Thromb. Vasc. Biol., 1996, 16, 1250-1255.
291. Dallongeville, J.; Lussier-Cacan, S.; Davignon, J. Modulation of plasma triglycerides levels by apoE phenotype: a meta-analysis. Lipid. Res., 1992, 33, 447-454.
292. Nikoulin, I.R.; Curtiss, L.K. An apolipoprotein E synthetic peptide targets to lipoproteins in plasma and mediates both cellular lipoprotein interactions in vitro and acute clearance of cholesterol-rich lipoproteins in vivo. J Clin. Invest., 1998, 101, 223-234.
293. Sungshin, Y.; Choi, S.; Allen, D.; Coopere, A. Comparison of the roles of the low density lipoprotein (ldl) receptor and thel dl receptor- related protein/aa-macroglobulin receptor in chylomicron remnant removal in the mouse in vivo. J. Biol. Chem., 1993, 268, 15804-15811.
294. Rumsey, S.C.; Galeano, N.F.; Lipschitz, B.; Deckelbaum, R.J. Oleate and other long chain fatty acids stimulate low density lipoprotein receptor activity by enhancing acyl coenzyme A: cholesterol acyltransferase activity and altering intracellular regulatory cholesterol pools in cultured cells. J. Biol. Chem., 1995, 270, 10008-10016.
295. Sakai, J.; Hoshino, A.; Takahashi, S.; Miura, Y.; Ishii, H.; Suzuki, H.; Kawarabayasi, Y.; Yamamoto, T. Structure, chromosome location, and expression of the human very low density lipoprotein receptor gene. J. Biol. Chem., 1994, 269, 2173-2182.
296. Dattaa, G.; Garbera, D.W.; Chunga, B.H.; Chaddhaa, M.; Dashtia, N.; Bradleya, W.A.; Gianturcoa, S.H.; Anantharamaiah, G.M. Cationic domain 141-150 of apoE covalently linked to a class A amphipathic helix enhances atherogenic lipoprotein metabolism in vitro and in vivo. J. Lipid. Res., 2001, 42, 959-966.
297. Jain, K.S.; Kathiravan M.K.; Somani R.S.; Shishoo C.J. The biology and chemistry of hyperlipidemia. Biorg. Med. Chem., 2007, 15, 4674-4699.