Lack of predictability of classical animal models for hypolipidemic activity: A good time for mice?

Atherosclerosis

Volumn 140, Issue 1, 1998, Pages 15-24

  Krause, Brian R ^a   Princen, Hans M G ^b  

^a PFIZER INC   (United States)

^b TNO   (Netherlands)

Author keywords

Classic models; HMG CoA reductase; Hypolipidemic activity

Indexed keywords

3 (2,4 DIFLUOROPHENYL) 1 HEPTYL 1 (4 NEOPENTYLBENZYL)UREA; ANTILIPEMIC AGENT; APOLIPOPROTEIN A1; ATORVASTATIN; AVASIMIBE; CHOLESTEROL ACYLTRANSFERASE INHIBITOR; FENOFIBRATE; FIBRIC ACID DERIVATIVE; GEMFIBROZIL; HIGH DENSITY LIPOPROTEIN; HIGH DENSITY LIPOPROTEIN RECEPTOR; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LOW DENSITY LIPOPROTEIN RECEPTOR; MEVINOLIN; NICOTINIC ACID; PD 148515; PHYTOSTEROL; PRAVASTATIN; PROBUCOL; RESIN; SIMVASTATIN; SULFAMIC ACID ((2,4,6 TRIS (1 METHYLETHYL) PHENYL)ACETYL) 2,6 BIS(1 METHYLETHYL) PHENYL ESTER; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ATHEROSCLEROSIS; CHOLESTEROL BLOOD LEVEL; CONTROLLED STUDY; DRUG DETERMINATION; DRUG MECHANISM; DRUG RESEARCH; DYSLIPIDEMIA; HUMAN; HYPOLIPEMIA; LIPOPROTEIN METABOLISM; MOUSE; NONHUMAN; PRIORITY JOURNAL; RAT; REVIEW;

ANIMALS; ANTILIPEMIC AGENTS; DISEASE MODELS, ANIMAL; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; HYPERLIPIDEMIAS; LIPIDS; LIPOPROTEINS; MICE; NIACIN;

EID: 0032171468     PISSN: 00219150     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0021-9150(98)00141-5     Document Type: Review

References (108)

1. Steinberg D Chemotherapeutic approaches to the problem of hyperlipidemia. Adv Pharmacol. 1:1962;59.
2. Bocan TMA Animal models of atherosclerosis and interpretation of drug intervention studies. Curr Pharm Des. 4:1998;39.
3. Krause BR, Newton RS Animal models for the evaluation of inhibitors of HMG-CoA reductase. Adv Lipids Res. 1:1991;57.
4. Endo A, Tsujita Y, Kuroda M, Tanzawa K Effects of ML-236B on cholesterol metabolism in mice and rats: lack of hypocholesterolemic activity in normal animals. Biochim Biophys Acta. 575:1979;266.
5. Tsujita Y, Kuroda M, Shimada Y, Tanzawa K, Arai M, Kaneko I, Tanaka M, Masuda H, Tarumi C, Watanabe Y CS-514, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase: tissue-selective inhibition of sterol synthesis and hypolipidemic effect on various animal species. Biochim Biophys Acta. 877:1986;50.
6. Fujioka T, Nara F, Tsujita Y, Fukushige J, Fukami M, Kuroda M The mechanism of lack of hypocholesterolemic effects of pravastatin sodium, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, in rats. Biochim Biophys Acta Lipids Lipid Metab. 1254:1995;7.
7. Krause BR, Bousley R, Kieft K, Robertson D, Stanfield R, Urda E, Newton RS Comparison of lifibrol to other lipid-regulating agents in experimental animals. Pharmacol Res. 29:1994;345.
8. Alberts AW, Chen J, Kuron G, Hunt V, Huff J, Hoffman C, Rothrock J, Lopez M, Joshua H, Harris E, Patchett A, Monaghan R, Currie S, Stapley E, Albers Schonberg G, Hensens O, Hirshfield J, Hoogsteen K, Liesch J, Springer J Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent. Proc Natl Acad Sci USA. 77:1980;3957.
9. Huff MW, Burnett JR 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and hepatic apo lipoprotein B secretion. Curr Opin Lipidol. 8:1997;138.
10. Krause BR, Newton RS Lipid-lowering activity of atorvastatin and lovastatin in rodent species: Triglyceride-lowering in rats correlates with efficacy in LDL animal models. Atherosclerosis. 117:1995;237.
11. Humble E, AL-Shurbaji A, Lund E, Berglund L Studies on rat liver phosphatidate phosphohydrolase and plasma lipids: effect of HMG-CoA reductase inhibitors. Biochim Biophys Acta Lipids Lipid Metab. 1214:1994;32.
12. Kritchevsky D, Tepper SA, Klurfeld DM Influence of mevinolin on experimental atherosclerosis in rabbits. Pharmacol Res Commun. 13:1981;921.
13. Kroon PA, Hand KM, Huff JW, Alberts AW The effects of mevinolin on serum cholesterol levels of rabbits with endogenous hypercholesterolemia. Atherosclerosis. 44:1982;41.
14. Chao YS, Yamin TT, Alberts AW Catabolism of low density lipoproteins by perfused rabbit livers: cholestyramine promotes receptor-dependent hepatic catabolism of low density lipoproteins. Proc Natl Acad Sci USA. 79:1982;3983.
15. Khosla P, Samman S, Carroll KK, Huff MW Turnover of 125I-VLDL and 131I-LDL apolipoprotein B in rabbits fed diets containing casein or soy protein. Biochim Biophys Acta. 1002:1989;157.
16. Chao YS, Yamin TT, Seidenberg J, Kroon PA Secretion of cholesteryl-ester-rich lipoproteins by the perfused livers of rabbits fed a wheat-starch-casein diet. Biochim Biophys Acta. 876:1986;392.
17. Krause BR, Pape ME, Kieft K, Auerbach B, Bisgaier CL, Homan R, Newton RS ACAT inhibition decreases LDL cholesterol in rabbits fed a cholesterol-free diet: Marked changes in LDL cholesterol without changes in LDL receptor mRNA abundance. Arterioscler Thromb. 14:1994;598.
18. Huff MW, Carroll KK Effects of dietary protein on turnover, oxidation and absorption of cholesterol, and on steroid excretion in rabbits. J Lipid Res. 21:1980;546.
19. Auerbach BJ, Krause BR, Bisgaier CL, Newton RS Comparative effects of HMG-CoA reductase inhibitors on apo B production in the casein-fed rabbit: Atorvastatin versus lovastatin. Atherosclerosis. 115:1995;173.
20. Bocan TMA, Mazur MJ, Mueller SB, Brown EQ, Sliskovic DR, O'Brien PM, Creswell MW, Lee H, Uhlendorf PD, Roth BD, Newton RS Antiatherosclerotic activity of inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase in cholesterol-fed rabbits: A biochemical and morphological evaluation. Atherosclerosis. 111:1994;127.
21. Quig DW, Zilversmit DB Dissociation between cholesterol secretion and plasma lipid transfer activity in rabbits. FASEB J. 2:1988;2712.
22. La Ville A, Moshy R, Turner PR, Miller NE, Lewis B Inhibition of cholesterol synthesis reduces low-density-lipoprotein apoprotein B production without decreasing very-low-density-lipoprotein apoprotein B synthesis in rabbits. Biochem J. 219:1984;321.
23. Ishida F, Sato A, Iizuka Y, Sawasaki Y, Aizawa A, Kamei T Effects of MK-733, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, on absorption and excretion of [3H]cholesterol in rabbits. Biochim Biophys Acta. 963:1988;35.
24. Ma PT, Gil G, Sudhof TC, Bilheimer DW, Goldstein JL, Brown MS Mevinolin, an inhibitor of cholesterol synthesis, induces mRNA for low density lipoprotein receptor in livers of hamsters and rabbits. Proc Natl Acad Sci USA. 83:1986;8370.
25. Otto J, Ordovas JM, Smith D, Van Dongen D, Nicolosi RJ, Schaefer EJ Lovastatin inhibits diet induced atherosclerosis in F1B Golden Syrian hamsters. Atherosclerosis. 114:1995;19.
26. Amin D, Gustafson S, Perrone MH Lovastatin is hypertriglyceridemic in Syrian golden hamsters. Biochem Biophys Res Commun. 157:1988;530.
27. Morand OH, Aebi JD, Dehmlow H, Ji YH, 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. 38:1997;373.
28. Spady DK, Dietschy JM Interaction of dietary cholesterol and triglycerides in the regulation of hepatic low density lipoprotein transport in the hamster. J Clin Invest. 81:1988;300.
29. Dvornik D, Cayen MN Drugs affecting lipoprotein disposition in laboratory animals. Fumagalli R, Kritchevsky D, Paoletti R Drugs Affecting Lipid Metabolism. 1980;263 Elsevier/North-Holland Biomedical Press, Amsterdam.
30. Rodney G, Uhlendorf P, Maxwell RE The hypolipidemic effect of gemfibrozil (CI-719) in laboratory animals. Proc roy Soc Med. 69:1976;6.
31. Stahlberg D, Angelin B, Einarsson K Effects of treatment with clofibrate, bezafibrate and ciprofibrate on the metabolism of cholesterol in rat liver microsomes. J Lipid Res. 30:1989;953.
32. Krause BR, Barnett BC, Essenburg AD, Kieft KA, Auerbach BJ, Bousley R, Stanfield R, Newton RS, Bisgaier CL Opposite effects of bezafibrate and gemfibrozil in both normal and hypertriglyceridemic rats. Atherosclerosis. 127:1996;91.
33. Haubenwallner S, Essenburg AD, Barnett BC, Pape ME, DeMattos RB, Krause BR, Minton LL, Auerbach BJ, Newton RS, Leff T, Bisgaier CL Hypolipidemic activity of select fibrates correlates to changes in hepatic apolipoprotein C-III expression: A potential physiologic basis for their mode of action. J Lipid Res. 36:1995;2541.
34. Newton RS, Krause BR Alterations in plasma high density lipoprotein levels with gemfibrozil treatment. Miller NE, Tall AR High Density Lipoproteins and Atherosclerosis III. 1992;259 Elsevier Scientific, Amsterdam.
35. Staels B, Van Tol A, Andreu T, Auwerx J Fibrates influence the expression of genes involved in lipoprotein metabolism in a tissue-selective manner in the rat. Arterioscler Thromb. 12:1992;286.
36. Pfeiffer M, Thiery J, Walli AK, Seidel D Gemfibrozil decreases cholesterol in the atherosclerotic aorta of rabbits (Abstract). Drugs Affecting Lipid Metabolism X. 127:1989.
37. Matsuoka N, Jingami H, Masuzaki H, Mizuno M, Nakaishi S, Suga J, Tanaka T, Yamamoto T, Nakao K Effects of gemfibrozil administration on very low density lipoprotein receptor mRNA levels in rabbits. Atherosclerosis. 126:1996;221.
38. Plancke MO, Olivier P, Clavey V, Marzin D, Fruchart JC Aspects of cholesterol metabolism in normal and hypercholesterolemic Syrian hamsters. Influence of fenofibrate. Methods Find Exp Clin Pharmacol. 10:1988;575.
39. Schoonjans K, Staels B, Auwerx J Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression. J Lipid Res. 37:1996;907.
40. Staels B, Auwerx J Role of PPAR in the pharmacological regulation of lipoprotein metabolism by fibrates and thiazolidinediones. Current Pharm Design. 3:1997;1.
41. Staels B, Vu-Dac N, Kosykh VA, Saladin R, Fruchart J-C, Dallongeville J, Auwerx J Fibrates downregulate apolipoprotein C-III expression independent of induction of peroxisomal acyl coenzyme A oxidase. A potential mechanism for the hypolipidemic action of fibrates. J Clin Invest. 95:1995;705.
42. Berthou L, Duverger N, Emmanuel F, Langouet S, Auwerx J, Guillouzo A, Fruchart J-C, Rubin E, Denefle P, Staels B, Branellec D Opposite regulation of human versus mouse apolipoprotein A-I by fibrates in human apolipoprotein A-I transgenic mice. J Clin Invest. 97:1996;2408.
43. Schoonjans K, Peinado-Onsurbe J, Lefebvre AM, Heyman RA, Briggs M, Deeb S, Staels B, Auwerx J PPARα and PPARgamma activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene. EMBO J. 15:1996;5336.
44. Lefebvre AM, Peinado-Onsurbe J, Leitersdorf I, Briggs MR, Paterniti Jr J, Fruchart J-C, Fievet C, Auwerx J, Staels B Regulation of lipoprotein metabolism by thiazolidinediones occurs through a distinct but complementary mechanism relative to fibrates. Arterioscler Thromb Vasc Biol. 17:1997;1756.
45. Lefebvre AM, Peinado-Onsurbe J, Leitersdorf I, Briggs MR Thiazolidinediones exert a hypotriglyceridemic effect by a distinct, but complementary mechanism relative to fibrates. Atherosclerosis. 134:1997;57.
46. Stafford RS, Blumenthal D, Pasternak RC Variations in cholesterol management practices of U.S. physicians. J Am Coll Cardiol. 29:1997;139.
47. Cayen MN, Kallai Sanfacon MA, Dubuc J, Greselin E, Dvornik D Evaluation of the lipid-lowering activity of AY-25,712 in rats. Atherosclerosis. 45:1982;267.
48. Muller KR, Cortesi RG The value of the normolipidaemic rat as an experimental animal in hypocholesterolemic drug research. Artery. 4:1978;564.
49. Ohata I, Sakamoto N, Nitatori R, Maeno H Aminophenyl ether compound (YM-95831), a new hypolipidemic agent with a high density lipoprotein elevating activity in rats. Arzneim-Forsch. 33:1983;237.
50. Magide AA, Myant NB Effect of nicotinic acid on cholesterol metabolism in monkeys. Clin Sci Mol Med. 46:1974;527.
51. Bentzen C, Guyon Y, Niesor E Nicotinic acid decreases specifically plasma Lp(a) in cynomolgus monkeys without affecting other lipoproteins. Atherosclerosis. 134:1997;137.
52. Merrill JM, Lemley-Stone J Effects of nicotinic acid on serum and tissue cholesterol in rabbits. Circ Res. 5:1957;617.
53. Cighetti G, Bosisio E, Galli G, Kienle MG The effect of cholestyramine on liver HMG-CoA reductase and cholesterol 7-alpha-hydroxylase in various laboratory animals. Life Sci. 33:1983;2483.
54. Maxwell RE, Nawrocki JW, Uhlendorf PD Some comparative effects of gemfibrozil, clofibrate, bezafibrate, cholestyramine and compactin on sterol metabolism in rats. Atherosclerosis. 48:1983;195.
55. Groot PHE, Pearce NJ, Suckling KE, Eisenberg S Effects of cholestyramine on lipoproteins and metabolism in Syrian hamsters. Biochim Biophys Acta. 23:1992;76-88.
56. Benson GM, Alston DR, Bond BC, Gee AN, Glen A, Haynes C, Hickey DMB, Iqbal S, Jackson B, Jaxa-Chamiec AA, Johnson MR, Roberts MG, Slingsby BP, Whittaker CM, Suckling KE SK&F 97426-A, a more potent bile acid sequestrant and hypocholesterolemic agent than cholestyramine in the hamster. Atherosclerosis. 101:1993;51.
57. Kowala MC, Nunnari JJ, Durham SK, Nicolosi RJ Doxazosin and cholestyramine similarly decrease fatty streak formation in the aortic arch of hyperlipidemic hamsters. Atherosclerosis. 91:1991;35.
58. Huff JW, Gilfillan JL, Hunt HJ Effect of cholestyramine, a bile acid binding polymer, on plasma cholesterol and fecal bile acid excretion in the rat. Proc Soc Exp Biol Med. 114:1963;352.
59. Auerbach B, Bousley R, Stanfield R, Bisgaier CL, Homan R, Krause BR Modulation of apoB kinetics and lipoprotein cholesterol in casein-fed rabbits by CI-1011: in vivo evidence for liver ACAT inhibition. Int Symp Drugs Affecting Lipid Met :Nov. 7-10:1995;135.
60. Lee HT, Sliskovic DR, Picard JA, Roth BD, Wierenga W, Hicks JL, Bousley RF, Hamelehle KL, Homan R, Speyer C, Stanfield RL, Krause BR Inhibitors of acyl-CoA: cholesterol O-acyl transferase (ACAT) as hypocholesterolemic agents. CI-1011: an acyl sulfamate with unique cholesterol-lowering activity in animals fed noncholesterol-supplemented diets. J Med Chem. 39:1996;5031.
61. Krause BR, Auerbach BJ ACAT inhibition by CI-1011 lowers plasma triglycerides in rats by enhancing the clearance of VLDL (Abstract). Atherosclerosis. 134:1997;128.
62. Ramharack R, Spahr MA, Sekerke C, Stanfield R, Bousley R, Lee H, Krause BR CI-1011 lowers lipoprotein(a) and plasma cholesterol concentrations in chow-fed cynomlgus monkeys. Atherosclerosis. 136:1997;79.
63. Harris WS, Dujovne C, Von Bergmann K, Neal J, Akester J, Windsor MT, Greene D, Look Z Effects of the ACAT inhibitor CL 277,082 on cholesterol metabolism in humans. Clin Pharmacol Ther. 48:1990;189.
64. Vora J, Stern R, Lathia C Clinical pharmacokinetics of CI-1011, an ACAT inhibitor. Pharm Res. 14:1997;505.
65. Krause BR, Bocan TMA ACAT inhibitors: physiologic mechanisms for hypolipidemic and anti-atherosclerotic activities in experimental animals. Ruffolo RR, Hollinger MA Inflammation: Mediators and Pathways. 1995;173 CRC Press, Boca Raton, FL.
66. Krause BR, Sliskovic DR, Bocan T Emerging therapies in atherosclerosis. Exp Opin Invest Drugs. 4:1995;353.
67. Matsuda K ACAT inhibitors as antiatherosclerotic agents: compounds and mechanisms. Med Res Rev. 14:1994;271.
68. Bocan TMA, Rosebury WS, Bak Mueller S, Milad M, Lathia C, Homan R Might ACAT inhibitors promote development of a stable plaque morphology? Circulation. 96:1997;491.
69. Nicolosi RJ, Wilson TA, Krause BR The ACAT inhibitor, CI-1011, is effective in the prevention and regression of early atherosclerosis in hamsters. Atherosclerosis. 137:1998;77.
70. Smith JD, Breslow JL The emergence of mouse models of atherosclerosis and their relevance to clinical research. J Int Med. 242:1997;99.
71. Plump A Atherosclerosis and the mouse: a decade of experience. Ann Med. 29:1997;193.
72. Berthou L, Duverger N, Emmanuel F, Langouet S, Auwerx J, Guillouzo A, Fruchart J-C, Rubin E, Denèfle P, Staels B, Branellec D Opposite regulation of human versus mouse apolipoprotein A-I by fibrates in human apolipoprotein A-I transgenic mice. J Clin Invest. 97:1996;2408.
73. Olivier P, Plancke MO, Marzin D, Clavey V, Sauzieres J, Fruchart J-C Effects of fenofibrate, gemfibrozil and nicotinic acid on plasma lipoprotein levels in normal and hyperlipidemic mice. Atherosclerosis. 70:1988;107.
74. Hayek T, Chajek-Shaul T, Walsh A, Azrolan N, Breslow J Probucol decreases apolipoprotein A-I transport rate and increases high density lipoprotien cholesteryl ester fractional catabolic rate in control and human apolipoprotein A-I transgenic mice. Arterio Thromb. 11:1991;1295.
75. Shepard J, Packard CJ, Morgan HG, Third JLHC, Stewart JM, Lawrie TDV The effects of cholestyramine on high density lipoprotein metabolism. Atherosclerosis. 33:1979;433.
76. Frazer KA, Narla G, Zhang JL, Rubin EM The apolipoprotein(a) gene is regulated by sex hormones and acute-phase inducers in YAC transgenic mice. Nat Genet. 9:1995;424.
77. Linton MF, Farese Jr RV, Chiesa G, Grass DS, Chin P, Hammer RE, Hobbs HH, Young SG Transgenic mice expressing high plasma concentrations of human apolipoprotein B100 and lipoprotein(a). J Clin Invest. 92:1993;3029.
78. Callow MJ, Stoltzfus LJ, Lawn RM, Rubin EM Expression of human apolipoprotein B and assembly of lipoprotein(a) in transgenic mice. Proc Natl Acad Sci USA. 91:1994;2130.
79. Zysow BR, Kauser K, Lawn RM, Rubanyi GM Effects of estrus cycle, ovariectomy, and treatment with estrogen, tamoxifen and progesterone on apolipoprotein(a) gene expression in transgenic mice. Arterio Thromb Vasc Biol. 17:1997;1741.
80. Shewmon DA, Stock JL, Rosen CJ, Heiniluoma KM, Hogue MM, Morrison A, Doyle EM, Ukena T, Weale V, Baker S Tamoxifen and estrogen lower circulating lipoprotein(a) concentrations in healthy postmenopausal women. Arterioscler Thromb. 14:1994;1586.
81. Ramires JAF, Mansur AP, Solimene MC, Maranhao R, Chamone D, da Luz P, Pileggi F Effect of gemfibrozil versus lovastatin on increased serum lipoprotein(a) levels of patients with hypercholesterolemia. Int J Cardiol. 48:1995;115.
82. Gurakar A, Hoeg JM, Kostner GM, Papadopoulos NM, Brewer HB Levels of lipoprotein(a) decline with neomycin and niacin treatment. Atherosclerosis. 57:1985;293.
83. Ramharack R, Spahr MA, Hicks GW, Kieft KA, Brammer DW, Minton LL, Newton RS Gemfibrozil significantly lowers cynomolgus monkey plasma lipoprotein[a]-protein and liver apolipoprotein[a] mRNA levels. J Lipid Res. 36:1995;1294.
84. Plump AS, Smith JD, Hayek T, Aalto Setala K, Walsh A, Verstuyft JG, Rubin EM, Breslow JL Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell. 71:1992;343.
85. Zhang SH, Reddick RL, Piedrahita JA, Maeda N Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. Science. 258:1992;468.
86. Van Ree JH, Van den Broek WJAA, Dahlmans VEH, Groot PHE, Vidgeon-Hart M, Frants RR, Wieringa B, Havekes LM, Hofker MH Diet-induced hypercholesterolemia and atherosclerosis in heterozygous apolipoprotein E-deficient mice. Atherosclerosis. 111:1994;25.
87. Zhang SH, Reddick RL, Avdievich E, Suries LK, Jones RG, Reynolds JB, Quarfordt SH, Maeda N Paradoxical enhancement of atherosclerosis by probucol treatment in apolipoprotein E-deficient mice. J Clin Invest. 99:1997;2858.
88. Tangirala RK, Casanada F, Miller E, Witztum JL, Steinberg D, Palinski W Effect of the antioxidant N,N'-diphenyl 1,4-phenylenediamine (DPPD) on atherosclerosis in apo E-deficient mice. Arterioscler Thromb Vasc Biol. 15:1995;1625.
89. Yamamoto A, Hara H, Takaichi S, Wakasugi J, Tamikawa M Effect of probucol on macrophages, leading to regression of xanthomas and atheromatous vascular lesions. Am J Cardiol. 62:1988;31B.
90. Moghadasian MH, McManus BM, Pritchard H, Frohlich J 'Tall oil'-derived phytosterols reduce atherosclerosis in apo E-deficient mice. Arterioscler Thromb Vasc Biol. 17:1997;119.
91. Homan R, Krause BR Established and emerging strategies for inhibition of cholesterol absorption. Curr Pharm Design. 3:1997;29.
92. Bourassa PAK, Milos PM, Gaynor BJ, Breslow JL, Aiello RJ Estrogen reduces atherosclerotic lesion development in apolipoprotein E-deficient mice. Proc Natl Acad Sci USA. 93:1996;10022.
93. Reckless J, Metcalfe JC, Grainger DJ Tamoxifen decreases cholesterol sevenfold and abolishes lipid lesion development in apolipoprotein E knockout mice. Circulation. 95:1997;1542.
94. Van Vlijmen BJM, Van den Maagdenberg AMJM, Gijbels MJJ, Van der Boom H, HogenEsch H, Frants RR, Hofker MH, Havekes LM Diet-induced hyperlipoproteinemia and atherosclerosis in apolipoprotein E3-Leiden transgenic mice. J Clin Invest. 93:1994;1403.
95. Van Vlijmen BJM, Van't Hof HB, Mol MJTM, Van der Boom H, Van der Zee A, Frants RR, Hofker MH, Havekes LM Modulation of very low density lipoprotein production and clearance contributes to age- and gender-dependent hyperlipoproteinemia in apolipoprotein E3-Leiden transgenic mice. J Clin Invest. 97:1996;1184.
96. Groot PHE, Van Vlijmen BJM, Benson GM, Hofker MH, Schiffelers R, Vidgeon-Hart M, Havekes LM Quantitative assessment of aortic atherosclerosis in APO E7z.ast;3 Leiden transgenic mice and its relationship to serum cholesterol exposure. Arterioscler Thromb Vasc Biol. 16:1996;926.
97. Van Vlijmen BJM, Mensink RP, Van't Hof HB et al. Effects of dietary fish oil on serum lipids and VLDL kinetics in hyperlipidemic apolipoprotein E*3-Leiden transgenic mice. J Lipid Res. 39:1998;1181-1188.
98. Van Vlijmen BJM, Pearce NJ, Bergo M, Staels B, Yates JW, Gribble AD, Bond BC, Hofker MH, Havekes L, Groot PHE Apolipoprotein E3-Leiden transgenic mice as test model for hypolipidaemic drugs. Arzneimittel. 48:1998;396.
99. Kesaniemi YA, Grundy SM Influence of gemfibrozil and clofibrate on metabolism of cholesterol and plasma triglycerides in man. J Am Med Assoc. 251:1984;2241.
100. Arad Y, Ramakrishnan R, Ginsberg HN Effects of lovastatin therapy on very-low-density lipoprotein triglyceride metabolism in subjects with combined hyperlipidemia: evidence for reduced assembly and secretion of triglyceride-rich lipoproteins. Metabolism. 41:1992;487.
101. Bisgaier CL, Essenburg AD, Auerbach B, Pape M, Sekerke C, Gee A, Wolle S, Newton RS Attenuation of plasma low density lipoprotein cholesterol by select 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in mice devoid of low density lipoprotein receptors. J Lipid Res. 38:1997;2502.
102. Arad Y, Ramakrishnan R, Ginsberg HN Lovastatin therapy reduces low density lipoprotein apo B levels in subjects with combined hyperlipidemia by reducing the production of apo B-containing lipoproteins: implications for the pathophysiology of apo B production. J Lipid Res. 31:1990;567.
103. Grundy SM, Vega GL Influence of mevinolin on metabolism of low density lipoproteins in primary moderate hypercholesterolemia. J Lipid Res. 26:1985;1464.
104. Marais AD, Firth JC, Bateman ME, Byrnes P, Martens C, Mountney J Atorvastatin: an effective lipid-modifying agent in familial hypercholesterolemia. Arterioscler Thromb Vasc Biol. 17:1997;1527.
105. Meiner VL, Cases S, Myers HM, Sande ER, Bellosta S, Schambelan M, Pitas RE, McGuire J, Herz J, Farese Jr RV Disruption of the acyl-CoA:cholesterol acyltransferase gene in mice: Evidence suggesting multiple cholesterol esterification enzymes in mammals. Proc Natl Acad Sci USA. 93:1996;14041.
106. Chang CCY, Huh HY, Cadigan KM, Chang TY J Biol Chem. 268:1993;20 747.
107. Krause BR, Anderson M, Bisgaier CL, Bocan T, Bousley R, DeHart P, Essenburg A, Hamelehle K, Homan R, Kieft K In vivo evidence that the lipid-regulating activity of the ACAT inhibitor CI-976 in rats is due to inhibition of both intestinal and liver ACAT. J Lipid Res. 34:1993;279.
108. Carr TP, Hamilton Jr RL, Rudel LL ACAT inhibitors decrease secretion of cholesteryl esters and apolipoprotein B by perfused livers of African green monkeys ACAT inhibitors decrease secretion of cholesteryl esters and apolipoprotein B by perfused livers of African green monkeys. J Lipid Res. 36:1995;25.