Lapaquistat acetate, a squalene synthase inhibitor, changes macrophage/lipid-rich coronary plaques of hypercholesterolaemic rabbits into fibrous lesions

British Journal of Pharmacology

Volumn 154, Issue 5, 2008, Pages 949-957

  Shiomi, M ^a   Yamada, S ^a   Amano, Y ^b   Nishimoto, T ^b   Ito, T ^a  

^a KOBE UNIVERSITY SCHOOL OF MEDICINE   (Japan)

^b TAKEDA PHARMACEUTICAL COMPANY LIMITED   (Japan)

Author keywords

Coenzyme Q10; Coronary atherosclerosis; Hypolipidemic effects; Lapaquistat acetate; Macrophages; Matrix metalloproteinase; Oxidized LDL; Squalene synthase inhibitor; WHHLMI rabbits

Indexed keywords

APOLIPOPROTEIN B100; COLLAGEN; INTERSTITIAL COLLAGENASE; LAPAQUISTAT ACETATE; PLASMINOGEN ACTIVATOR INHIBITOR 1; SQUALENE SYNTHASE INHIBITOR; TAK 475; UBIDECARENONE; VERY LOW DENSITY LIPOPROTEIN CHOLESTEROL;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; ATHEROSCLEROTIC PLAQUE; CHOLESTEROL BLOOD LEVEL; CONTROLLED STUDY; CORONARY ARTERY ATHEROSCLEROSIS; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG MECHANISM; DRUG MEGADOSE; HEART INFARCTION; HISTOPATHOLOGY; HYPERCHOLESTEROLEMIA; IMAGE ANALYSIS; IMMUNOHISTOCHEMISTRY; LIPID BLOOD LEVEL; LOW DRUG DOSE; MACROPHAGE; MALE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RABBIT; TRIACYLGLYCEROL BLOOD LEVEL; XANTHOMA;

ANIMALS; ANTILIPEMIC AGENTS; APOLIPOPROTEIN B-100; CHOLESTEROL; COLLAGEN; CORONARY ARTERY DISEASE; DISEASE MODELS, ANIMAL; DISEASE PROGRESSION; DOSE-RESPONSE RELATIONSHIP, DRUG; ENZYME INHIBITORS; FARNESYL-DIPHOSPHATE FARNESYLTRANSFERASE; HYPERCHOLESTEROLEMIA; IMAGE INTERPRETATION, COMPUTER-ASSISTED; IMMUNOHISTOCHEMISTRY; LIPID METABOLISM; LIPOPROTEINS, LDL; MACROPHAGES; MALE; MATRIX METALLOPROTEINASE 1; OXAZEPINES; PIPERIDINES; PLASMINOGEN ACTIVATOR INHIBITOR 1; RABBITS; TRIGLYCERIDES; UBIQUINONE; XANTHOMATOSIS;

EID: 46249091114     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1038/bjp.2008.143     Document Type: Article

References (37)

1. Adans JA, Economou AP, Martinson Jr JM, Zhou M, Wahl LM (2002). Oxidized low-density and high-density lipoproteins regulate the production of matrix metalloproteinase-1 and -9 by activated monocytes. J Leukoc Biol 71: 1012-1018.
2. Amano Y, Nishimoto T, Tozawa R, Ishikawa E, Imura Y, Sugiyama Y (2003). Lipid-lowering effects of TAK-475, a squalene synthase inhibitor, in animal models of familial hypercholesterolemia. Eur J Pharmacol 466: 155-161.
3. Bergstrom JD, Kurtz MM, Rew DJ, Amend AM, Karkas JD, Bostedor RG et al. (1993). Zaragozic acids: a family of fungal metabolites that are picomolar competitive inhibitors of squalene synthase. Proc Natl Acad Sci USA 90: 80-84.
4. Blum A, Simsolo C, Hasin Y (2004). 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), atherosclerosis and coronary syndromes. Atherosclerosis 175: 1-5.
5. Davies MJ (1996). Stability and instability: two faces of coronary atherosclerosis. Circulation 94: 2013-2020.
6. Fukumoto Y, Libby P, Rabkin E, Hill CC, Enomoto M, Hirouchi Y et al. (2001). Statins alter smooth muscle cell accumulation and collagen content in established atheroma of Watanabe heritable hyperlipidemic rabbits. Circulation 103: 993-999.
7. Goldstein JL, Kita T, Brown MS (1983). Defective lipoprotein receptors and atherosclerosis: lessons from an animal counterpart of familial hypercholesterolemia. N Engl J Med 309: 288-296.
8. Hiroshima O, Shino M (1993). Determination of ubiquinones in biological material by high performance liquid chromatography. Nippon Rinsho 51: 952-958 (in Japanese).
9. Hiyoshi H, Yanagimachi M, Ito M, Ohtsuka I, Yoshida I, Saeki T et al. (2000). 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 41: 1136-1144.
10. Hiyoshi H, Yanagimachi M, Ito M, Yasuda N, Okada T, Ikuta H et al. (2003). Squalene synthase inhibitors suppress triglyceride biosynthesis through the farnesol pathway in rat hepatocytes. J Lipid Res 44: 128-135.
11. Itabe H, Takeshima E, Iwasaki H, Kimura J, Yoshida Y, Imanaka T et al. (1994). A monoclonal antibody against oxidized lipoprotein recognizes foam cells in atherosclerotic lesions. Complex formation of oxidized phosphatidylcholines and polypeptides. J Biol Chem 269: 15274-15279.
12. Ito T, Yamada S, Shiomi M (2004). Progression of coronary atherosclerosis relates to the onset of myocardial infarction in an animal model of spontaneous myocardial infarction (WHHLMI rabbits). Exp Anim 53: 339-346.
13. James AM, Smith RAJ, Murphy MO (2004). Antioxidant and prooxidant properties of mitochondorial coenzyme Q. Arch Biochem Biophys 423: 47-56.
14. Kita T, Yokode M, Watanabe Y, Narumiya S, Kawai C (1986). Stimulation of cholesteryl ester synthesis in mouse peritoneal macrophages by cholesterol-rich very low density lipoproteins from the Watanabe heritable hyperlipidemic rabbit, an animal model of familial hypercholesterolemia. J Clin Invest 77: 1460-1465.
15. Libby P, Aikawa M (2003). Mechanism of plaque stabilization with statins. Am J Cardiol 91: 4B-8B.
16. Miki T, Kori M, Mabuchi H, Tozawa R, Nishimoto T, Sugiyama Y et al. (2002). Synthesis of novel 4,1-benzoxazepine derivatives as squalene synthase inhibitors and their inhibitions of cholesterol synthesis. J Med Chem 45: 4571-4580.
17. Mohr D, Bowry VW, Stocker R (1992). Dietary supplementation with coenzyme Q10 results in increased levels of ubiquinol-10 within circulating lipoproteins and increased resistance of human low-density lipoprotein to the initiation of lipid peroxidation. Biochim Biophys Acta 1126: 247-254.
18. Naghavi M, Libby P, Falk E, Casscells SW, Litovsky S, Rumberger J et al. (2003). From vulnerable plaques to vulnerable patients, a call for new definitions and risk assessment strategies: part I. Circulation 108: 1664-1672.
19. Nakajima K, Nakano T, Tanaka A (2006). The oxidative modification hypothesis of atherosclerosis: the comparison of atherogenic effects on oxidized LDL and remnant lipoproteins in plasma. Clin Chim Acta 367: 36-47.
20. Nakazato K, Ishibashi T, Shindo J, Shiomi M, Maruyama Y (1996). Expression of very low density lipoprotein receptor mRNA in rabbit atherosclerotic lesions. Am J Pathol 149: 1831-1838.
21. Nishimoto T, Amano Y, Tozawa R, Ishikawa E, Imura Y, Yukimasa H et al. (2003). Lipid-lowering properties of TAK-475, a squalene synthase inhibitor, in vivo and in vitro. Br J Pharmacol 139: 911-918.
22. Nishimoto T, Ishikawa E, Anayama H, Hamajyo H, Nagai H, Hirakata M et al. (2007). Protective effects of a squalene synthase inhibitor, lapaquistat acetate (TAK-475), on statin-induced myotoxicity in guinea pigs. Toxicol Appl Pharmacol 223: 39-45.
23. Rapp JH, Lespine A, Hamilton RL, Colyvas N, Chaumeton AH, Tweedie-Hardman J et al. (1994). Triglyceride-rich lipoproteins isolated by selected-affinity anti-apolipoprotein B immunosorption from human atherosclerotic plaque. Arterioscler Thromb 14: 1767-1774.
24. Sever PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M et al. (2003). ASCOT investigators. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): a multicentre randomized controlled trial. Lancet 361: 1149-1158.
25. Shiomi M, Ito T, Hirouchi Y, Enomoto M (2001). Fibromuscular cap composition is important for the stability of established atherosclerotic plaques in mature WHHL rabbits treated with statins. Atherosclerosis 157: 75-84.
26. Shiomi M, Ito T, Shiraishi M, Watanabe Y (1992). Inheritability of atherosclerosis and the role of lipoproteins as risk factors in the development of atherosclerosis in WHHL rabbits: risk factors related to coronary atherosclerosis are different from those related to aortic atherosclerosis. Atherosclerosis 96: 43-52.
27. Shiomi M, Ito T, Tsukada T, Yata T, Ueda M (1994). Cell compositions of coronary and aortic atherosclerotic lesions differ: an immunohistochemical study. Arterioscler Thromb 14: 931-937.
28. Shiomi M, Ito T, Tsukada T, Yata T, Watanabe Y, Tsujita Y et al. (1995). Reduction of serum cholesterol levels alters lesional composition of atherosclerotic plaques: effect of pravastatin sodium on atherosclerosis in mature WHHL rabbits. Arterioscle Thromb Vasc Biol 5: 1938-1944.
29. Shiomi M, Ito T, Watanabe Y, Tsujita Y, Kuroda M, Arai M et al. (1990). Suppression of established atherosclerosis and xanthomas in mature WHHL rabbits by keeping their serum cholesterol levels extremely low: effect of pravastatin sodium in combination with cholestyramine. Atherosclerosis 83: 69-80.
30. Shiomi M, Ito T, Yamada S, Kawashima S, Fan J (2003). Development of an animal model for spontaneous myocardial infarction (WHHLMI rabbit). Arterioscler Thromb Vasc Biol 23: 1239-1244.
31. Shiomi M, Ito T, Yamada S, Kawashima S, Fan J (2004). Correlation of vulnerable coronary plaques to sudden cardiac events. Lessons from a myocardial infarction-prone animal model (the WHHLMI rabbit). J Atheroscler Thromb 11: 184-189.
32. Shiomi M, Yamada S, Ito T (2005). Atheroma stabilizing effects of simvastatin due to depression of macrophages or lipid accumulation in the atheromatous plaques of coronary atherosclerosis-prone WHHL rabbits. Atherosclerosis 178: 287-294.
33. Suzuki H, Kobayashi H, Sato F, Yonemitsu Y, Nakashima Y, Sueishi K (2003). Plaque-stabilizing effect of pitavastatin in Watanabe heritable hyperlipidemic (WHHL) rabbits. J Atheroscler Thromb 10: 109-116.
34. Tavridou A, Kaklamanis L, Papalois A, Kourounakis AP, Rekka EA, Kourounakis PN et al. (2007). EP2306, a novel squalene synthase inhibitor, reduces atherosclerosis in the cholesterol-fed rabbit. J Pharmacol Exp Ther 323: 794-804.
35. Tavridou A, Manolopoulos VG (2004). Antioxidant properties of two novel 2-biphenylmorpholine compounds (EP2306 and EP2301) in vitro and in vivo. Eur J Pharmacol 505: 213-221.
36. Watanabe Y (1980). Serial inbreeding of rabbits with hereditary hyperlipidemia (WHHL-rabbit). Atherosclerosis 36: 261-268.
37. Williams DA (1986). A note on Shirley's nonparametric test for comparing several dose levels with a zero-dose control. Biometrics 42: 183-186.