Guinea Pigs as Models to Study the Hypocholesterolemic Effects of Drugs

Cardiovascular Drug Reviews

Volumn 22, Issue 1, 2004, Pages 55-70

  West, Kristy L ^a   Fernandez, Maria Luz ^a  

^a UNIVERSITY OF CONNECTICUT   (United States)

Author keywords

ACAT; ASBT; Atherosclerosis; Bile acid sequestrants; Fibric acids; Guinea pigs; LDL cholesterol; Probucol; Statins

Indexed keywords

3 (2,4 DIFLUOROPHENYL) 1 HEPTYL 1 (4 NEOPENTYLBENZYL)UREA; APICAL SODIUM BILE ACID TRANSPORTER INHIBITOR; ATORVASTATIN; BILE ACID RESIN; CHOLESTEROL ACYLTRANSFERASE INHIBITOR; FIBRIC ACID DERIVATIVE; GEMFIBROZIL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; HYPOCHOLESTEROLEMIC AGENT; LIFIBROL; LOW DENSITY LIPOPROTEIN CHOLESTEROL; MEVINOLIN; PD 321301 2; PITAVASTATIN; PRAVASTATIN; PROBUCOL; RESIN; SIMVASTATIN; SQUALENE SYNTHASE INHIBITOR; STATINE DERIVATIVE; UNCLASSIFIED DRUG; YM 53601;

ANIMAL MODEL; ATHEROSCLEROSIS; CHOLESTEROL BLOOD LEVEL; CHOLESTEROL METABOLISM; DRUG EFFECT; DRUG MECHANISM; GUINEA PIG; HUMAN; HYPERCHOLESTEROLEMIA; NONHUMAN; OVARIECTOMY; PRIORITY JOURNAL; REVIEW; TREATMENT OUTCOME;

EID: 1642387019     PISSN: 08975957     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1527-3466.2004.tb00131.x     Document Type: Review

References (91)

1. Amin D, Rutledge RZ, Needle SN, et al. RPR 107393, a potent squalene synthase inhibitor and orally effective cholesterol-lowering agent: Comparison with inhibitors of HMG-CoA reductase. J Pharmacol Exp Ther 1997;281:746-752.
2. Angelin B, Olivecrona H, Reihner H, et al. Hepatic cholesterol metabolism in estrogen-treated men. Gastroenterology 1992;103:1657-1663.
3. Aoki T, Nishimura H, Nakagawa S, et al. Pharmacological profile of a novel synthetic inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Arzneimittelforschung 1997;47:904-909.
4. Aviram M, Rosenblat M, Bisgaier CL, Newton RS. Atorvastatin and gemfibrozil metabolites, but not the parent drugs, are potent antioxidants against lipoprotein oxidation. Atherosclerosis 1998;138:271-280.
5. Bakker-Arkema RG, Davidson MH, Goldstein RJ, et al. Efficacy and safety of a new HMG-CoA reductase inhibitor, atorvastatin, in patients with hypertriglyceridemia. J Am Med Assoc 1996;275:128-133.
6. Berglund L, Sharkey MF, Elam RL, Witztum JL. Effects of lovastatin therapy on guinea pig low density lipoprotein composition and metabolism. J Lipid Res 1989;30:1591-1600.
7. Berglund LF, Beltz WF, Elam RL, Witztum JL. Altered apolipoprotein B metabolism in very low density lipoprotein from lovastatin-treated guinea pigs. J Lipid Res 1994;35:956-965.
8. Bergstrom JD, Dufresne C, Bills GF, Nallin-Omstead M, Byrne K. Discovery, biosynthesis, and mechanism of action of the zaragozic acids: Potent inhibitors of squalene synthase. Annu Rev Microbiol 1995;49:607-639.
9. Berthou L, Duverger N, Emmanuel F, et al. Opposite regulation of human versus mouse apolipoprotein A-1 by fibrate in human apolipoprotein A-1 transgenic mice. J Clin Invest 1996;97:2408-2416.
10. Bilhartz LE, Spady DK, Dietschy JM. Inappropriate hepatic cholesterol synthesis expands the cellular pool of sterol available for recruitment by bile acids in the rat. J Clin Invest 1989;84:1181-1187.
11. Bruckert E. New advances in lipid-modifying therapies for reducing cardiovascular risk. Cardiology 2002;97:59-66.
12. Chao YS, Yamin TT, Alberts AW. Effects of cholestyramine on low density lipoprotein binding sites on liver membranes from rabbits with endogenous hypercholesterolemia induced by a wheat starch-casein diet. J Biol Chem 1982;257:3623-3627.
13. Chen F, Ma L, Al-Ansari N and Shneider B. The role of AP-1 in the transcriptional regulation of the rat apical sodium-dependent bile acid transporter. J Biol Chem 2001;276:38703-38714.
14. Ciosek Jr CP, Magnin DR, Harrity TW, et al. Lipophilic 1,1-bisphosphonates are potent squalene synthase inhibitors and orally active cholesterol lowering agents in vivo. J Biol Chem 1993;268:24832-24837.
15. Conde K, Vergara-Jimenez M, Krause BR, Newton RS, Fernandez ML. Hypocholesterolemic actions of atorvastatin are associated with alterations on hepatic cholesterol metabolism and lipoprotein composition in the guinea pig. J Lipid Res 1996;37:2372-2382.
16. Conde K, Pineda G, Newton RS, Fernandez ML. Hypocholesterolemic effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors in the guinea pig. Biochem Pharm 1999;58:1209-1219.
17. Conde K, Roy S, Freake HC, Newton RS, Fernandez ML. Atorvastatin and sinivastatin have distinct effects on hydroxyl methylglutaryl-CoA reductase activity and mRNA abundance in the guinea pig. Lipids 1999;34:1327-1332.
18. Dietschy JM, Turley SD and Spady DK. Role of the liver in the maintenance of cholesterol and low density lipoprotein homeostasis in different animal species, including humans. J Lipid Res 1993;34:1637-1659.
19. Dobs AS, Prasad M, Goldberg A, Guccione M, Hoover DR. Changes in serum lipoprotein(a) in hyperlipidemic subjects undergoing long-term treatment with lipid-lowering drugs. Cardiovasc Drugs Ther 1995;9:677-684.
20. Douglas G and Pownell JJ. Comparative specificity of plasma lecithin-cholesterol acyltransferase from ten animal species. Lipids 1991;26:416-420.
21. Einarsson K, Ericsson S, Ewerth S, et al. Effects of cholestyramine in plasma triglyceride concentrations in moderate hypercholesterolemic patients. Eur J Clin Pharmacol 1991;40:S53-S58.
22. Ensign WY, McNamara DJ, Fernandez ML. Exercise improves plasma lipid profiles and modifies lipoprotein composition in guinea pigs. J Nutr Biochem 2002;13:747-753.
23. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Circulation 1994;89:1329-1345.
24. Felgines C, Mazur A, Rayssiguier Y. Effect of the interruption of enterohepatic circulation of bile acids by cholestyramine on apolipoprotein gene expression in the rat. Life Sci 1994;55:1053-1060.
25. Fernandez ML, Yount NY, McNamara DJ. Whole body cholesterol synthesis in the guinea pig: Effects of dietary fat quality. Biochim Biophys Acta 1990;1044:340-348.
26. Fernandez ML, Ruiz LR, Conde AK, Sun C-M, Erickson S, McNamara DJ. Psyllium reduces plasma LDL in guinea pigs by altering hepatic cholesterol metabolism. J Lipid Res 1995;36:1128-1138.
27. Fernandez ML, Roy S, Vergara-Jimenez M. Resistant starch and cholystyramine have distinct effects on hepatic cholesterol metabolism in guinea pigs fed a hypercholesterolemic diet. Nutr Res 2000;20:837-849.
28. Fernandez ML. Guinea pigs as models for cholesterol and lipoprotein metabolism. J Nutr 2001;131:10-20.
29. Fruchart JC, Brewer HB, Leitersdorf E. Consensus for the use of fibrates in the treatment of dislipoproteinemia and coronary heart disease. Am J Cardiol 1998;81:912-917.
30. Ha YC, Barter PA. Differences in plasma cholesteryl ester transfer protein activity in sixteen vertebrate species. Comp Biochem Physiol 1982;71:265-269.
31. Haffner SM. Secondary prevention of coronary heart disease. The role of fibric acids. Circulation 2000;102:2-4.
32. Hasibeder H, Staab HJ, Seibel K, et al. The clinical pharmacology of K12.148 in healthy subjects. X International Symposium on Drugs Affecting Lipid Metabolism. 8-11 November 1989; Houston, TX, USA, p. 93.
33. Hassan AS, Gallon LS, Yunker RL, Subbiah MT. Effect of feeding β-sitosterol alone or in combination with cholystyramine during early life on subsequent response to cholesterol challenge in adult life in guinea pigs. Br J Nutr 1982;48:443-450.
34. Heel RC, Brogden RN, Speight TM, Avery GS. Probucol: A review of its pharmacological properties and therapeutic use in pharmacological properties and therapeutic use in patients with hyperholesterolaemia. Drugs 1978;15:409-428.
35. Hidaka K, Takada Y, Matsunaga A, Sasaki J, Arakawa K. Effects of probucol on low-density lipoprotein catabolism in guinea pigs. Artery 1992;19:162-176.
36. Hoffman R, Brook GJ, Aviram M. Hypolipidemic drugs reduce lipoprotein susceptibility to undergo lipid peroxidation: In vitro and ex vivo studies. Atherosclerosis 1992;93:105-113.
37. Howard AN, Zschocke R, Loser R, Hofrichter G. The hypocholesterolemic effect of terbufibrol and other drugs in normal and hypercholesterolemic baboons. Atherosclerosis 1979;32:367-380.
38. Hui DY, Innerarity TL, Mahley W. Lipoprotein binding to canine hepatic membranes. J Biol Chem 1981;256:5646-5655.
39. Insull W, Koren M, Davignon J, et al. Efficacy and short-term safety of a new ACAT inhibitor, avasimibe, on lipids, lipoproteins, and apolipoproteins, in patients with combined hyperlipidemia. Atherosclerosis 2001;157:137-144.
40. Junquero D, Oms P, Carilla-Durand E, et al. Pharmacological profile of F 12511, (S)-2′,3′,5′-trimethyl-4′-hydroxy-α -dodecylthioacetanilide a powerful and systemic acylcoenzyme A: Cholesterol acyltransferase inhibitor. Biochem Pharm 2001;61:97-108.
41. Kieft KA, Bocan TMA, Krause BR. Rapid on-line determination of cholesterol distribution among plasma lipoproteins after high-performance gel filtration chromatography. FASEB J 1990;4:A924.
42. Koga T, Shimada Y, Kuroda M, et al. Tissue-selective inhibition of cholesterol synthesis in vivo by pravastatin sodium, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. Biochim Biophys Acta 1990;1045:115-120.
43. Koga T, Fukuda K, Shimada Y, et al. Tissue selectivity of pravastatin sodium, lovastatin and simvastatin. The relationship between inhibition of de novo sterol synthesis and active drug concentrations in the liver, spleen and lestis in rat. Eur J Biochem 1992;209:315-319.
44. Koga T, Kikuchi T, Miyazaki A, et al. Tissue-selective inhibition of sterol synthesis in mice by pravastatin sodium after a single or repeated oral administrations. Lipids 1995;30:775-779.
45. Krause BR, Newton RS. Animal models for the evaluation of inhibitors of HMG-CoA reductase. Adv Lipid Res 1991;1:57-72.
46. Krause BR, Black A, Bousley R, et al. Divergent pharmacologic activities of PD 321301-2 and CL 277.082. urea inhibitors of Acyl-CoA:Cholesterol Acyltransferase. J Pharm Exp Ther 1993;267:734-743.
47. Krause BR, Bousley R, Kieft K, et al. Comparison of lifibrol to other lipid-lowering agents in experimental animals. Pharmacol Res 1994;29:345-357.
48. 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 1995;117:237-244.
49. Levy R, Langer T. Hypolipidemic drugs and lipoprotein metabolism. Adv Exp Med Biol 1972;26:155-163.
50. Li JR, Bale LK, Subbiah MT. Effect of enhancement of cholesterol degradation during neonatal life of guinea pig on its subsequent response to dietary cholesterol. Atherosclerosis 1979;32:93-98.
51. Lindenthal B, Bertsch T, Fassbender K, et al. Influence of simvastatin, pravastatin, and BM 15.766 on neutral sterols in liver and testis of guinea pigs. Metabolism 2002;15:492-499.
52. Ma PTS, 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 1986;83:8370-8374.
53. Matsunaga A, Sasaki J, Takada Y, Hidaka K, Arakawa K. Effect of simvastatin on receptor mediated metabolism of low density lipoprotein in guinea pigs. Atherosclerosis 1991;90:31-37.
54. Matsunaga A, Sasaki J, Hidaka K, et al. Pravastatin-induced changes in receptor-mediated metabolism on low density lipoprotein in guinea pigs. Artery 1994;21:94-113.
55. McNamara DJ. Cholesterol homeostasis in the guinea pig. The importance of quantitating net tissue accumulation of cholesterol in sterol balance studies. Biochim Biophys Acta 1984;796:51-54.
56. Nakao K, Kubota H, Yasuhara M, et al. Novel hydroxyphenylurea dual inhibitor against acyl-CoA:cholesterol acyltransferase (ACAT) and low density lipoprotein (LDL) oxidation as antiatherosclerotic agent. Bioorg Med Chem 2001;9:853-861.
57. Naoumova RP, Dunn S, Rallidis L, et al. Prolonged inhibition of cholesterol synthesis explains the efficiency of atorvastatin. J Lipid Res 1997;38:1496-1500.
58. Naruswicz M, Carew TE, Pittman RC, Witztum JL, Steinberg D. A novel mechanism by which probucol lowers low density lipoprotein levels demonstrated in the LDL receptor-deficient rabbit. J Lipid Res 1984;25:1206-1213.
59. Nawrocki JW, Weiss SR, Davidson MH, et al. Reductions of LDL cholesterol by 25% and 60% in patients with primary hypercholesterolemia by atorvastatin, a new HMG-CoA reductase inhibitor. Atheroscler Thromb Vasc Biol 1995;15:678-682.
60. Neinonen T, Stein E, Weiss SR, McKenney JM, Davidson M, Shurzinske L. The lipid-lowering effects of atorvastatin, a new HMG-CoA reductase inhibitor: Results of a randomized, double masked study. Clin Ther 1996;18:853-863.
61. Nicolosi RJ. Dietary fat saturation effects on low-density-lipoprotein concentrations and metabolism in various animal models. Am J Clin Nutr 1997;65(Suppl):1617S-1627S.
62. Olivecrona T, Bengsston-Olivecrona G. Lipoprotein lipase and hepatic lipase. Curr Opin Lipidiol 1993;4:187-196.
63. Peters JM, Hennuyer N, Staels B, et al. Alterations in lipoprotein metabolism in peroxisome proliferator-activated receptor α-deficient mice. J Biol Chem 1997;272:27307-27312.
64. Popjak G, Agnew WS. Squalene synthase. Mol Cell Biochem 1979;27:97-116.
65. Rapp SR, Bhat BG, Beaudry JA, Napawan N, Keller BT. SC-435 is a potent inhibitor of the apical sodium co-dependent bile acid transporter (ASBT) in mice, rats, hamsters and dogs and reduces atherosclerotic lesions in apoE-/- mice. DALM 2001;abstr 50.
66. Reihner E, Angelin B, Rudling M, Ewerth S, Bjorkhem I, Einarsson K. Regulation of hepatic cholesterol metabolism in humans: Stimulatory effects of cholestyramine on HMG-CoA reductase activity and low density lipoprotein receptor expression in gallstone patients. J Lipid Res 1990;31:2219-2226.
67. Reihner E, Angelin B, Bjorkhem I and Einarsson K. Hepatic cholesterol metabolism in cholesterol gallstone disease. J Lipid Res 1991;32:469-475.
68. Roth BD, Bocan TM, Blankley CJ, et al. Relationship between tissue selectivity and lipophilicity for inhibitors of HMG-CoA reductase. J Med Chem 1991;34:463-466.
69. Roy S, Vega-Lopez S, Fernandez ML. Gender and hormonal status affect the hypolipidemic mechanisms of dietary soluble fiber in guinea pigs. J Nutr 2000;130:600-607.
70. Rubins HB, Robins SJ, Collins D, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol: Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 1999;341:410-418.
71. γ activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene. EMBO J 1996;15:5336-5348.
72. Shneider BL, Dawson PA, Christie DM, Hardikar W, Wong MH, Suchy FJ. Cloning and molecular characterization of the ontogeny of a rat ileal sodium-dependent bile acid transporter. J Clin Invest 1995;95:745-754.
73. Slater HR, Packard CJ, Bicker S, Shepherd J. Effects of cholestyramine on receptor-mediated plasma clearance and tissue uptake of human low density lipoproteins in the rabbit. J Biol Chem 1980;265:10210-10213.
74. Sloop CH, Dory L, Krause BR, Castle C, Roheim PS. Lipoproteins and apolipoproteins in peripheral lymph of normal and cholesterol-fed dogs. Atherosclerosis 1983;49:9-21.
75. Smith SA. Peroxisomal proliferators activated receptors (PPARs): molecular targets for hypolipidaemic agents and insulin sensitizers. Pharmacol Rev Commun 1996;8:57-64.
76. Staels B, Vu-Dac N, Kosykh VA, et al. 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 1995;95:705-712.
77. Suzuki H, Aoki T, Tamaki T, Sato F, Kitahara M, Saito Y. Hypolipidemic effect of NK-104, a potent HMG-CoA reductase inhibitor, in guinea pigs. Atherosclerosis 1999;146:259-270.
78. Swann A, Wiley MH, Sipperstein MD. Tissue distribution of cholesterol feedback control in the guinea pig. J Lipid Res 1975;16:360-366.
79. The BIP Study Group. Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease: The Benzafibrate Infarction Prevention (BIP) study. Circulation 2000;102:21-27.
80. Turley SD, West CE. Effect of cholesterol and cholestyramine feeding and of fasting on sterol synthesis in the liver, ileum and lung of the guinea pig. Lipids 1976;11:571-577.
81. Ugawa T, Kakuta H, Moritani H, et al. YM-53601, a novel squalene synthase inhibitor, reduces plasma cholesterol and triglyceride levels in several animal species. Br J Pharmacol 2000;131:63-70.
82. Vazquez M, Alegret M, Lopez M, et al. Different effects of fibrates on the microsomal fatty acid chain elongation and the acyl composition of phospholipids in guinea pigs. Br J Pharmacol 1995;116:3337-3343.
83. West KL, Ramjiganesh T, Roy S, Keller BT, Fernandez ML. 1-[4-[4[(4R,5R)-3,3-Dibutyl-7-(dimethylamino)-2,3,4,5-tetrahydro-4-hydroxy-1, 1-dioxido-1-benzothiepin-5-yl]phenoxy]butyl]-4-aza-1-azoniabicyclo[2.2.2]octane methanesulfonate (SC-435), an ileal apical sodium-codependent bile acid transporter inhibitor alters hepatic cholesterol metabolism and lowers plasma low-density lipoprotein-cholesterol concentrations in guinea pigs. J Pharmacol Exp Ther 2002;303:293-299.
84. West KL, Zern TL, Butteiger DN, Keller BT, Fernandez ML. SC-435, an ileal apical sodium co-dependent bile acid transporter (ASBT)inhibitor lowers plasma cholesterol and reduces atherosclerosis in guinea pigs. Atherosclerosis 2003;171:201-210.
85. Witztum JL, Schonfeld G, Weidman SW. The effects of colestipol on the metabolism of very low density lipoproteins in man. J Lab Clin Med 1976;88:1008-1018.
86. Witztum JL, Schonfeld G, Weidman SW, Giese WE, Dillingham MA. Bile acid sequestrant therapy alters the composition of low density and high density lipoproteins. Metabolism 1979;28:221-229.
87. Witztum JL, Young SG, Elam RL, Carew TE, Fisher M. Cholestyramine-induced changes in low density lipoprotein composition and metabolism. 1. Studies in the guinea pig. J Lipid Res 1985;26:92-103.
88. Wong MH, Oelkers P, Dawson PA. Identification of a mutation in the ileal sodium-dependent bile acid transporter gene that abolishes transport activity. J Biol Chem 1995;270:27228-34.
89. Xu G, Shneider BL, Shefer S, et al. Ileal bile acid transport regulates bile acid pool, synthesis, and plasma cholesterol levels differently in cholesterol-fed rats and rabbits. J Lipid Res 2000;41:298-304.
90. Yamada Y, Goto Y, Saito Y, NK-104 Clinical Evaluation Committee. Clinical effect of NK-104 (Nisvastatin) on hyperlipidemia - double-blind comparative dose-finding study in three parallel groups. Proceedings of the XIII International Symposium on Drugs Affecting Lipid Metabolism 1998;129 (abstract).
91. +-independent multispecific anion transporter mediates active transport of pravastatin into rat liver. Am J Physiol 1993;264:G36-G44.