Pyripyropene A, an acyl-coenzyme a: Cholesterol acyltransferase 2-selective inhibitor, attenuates hypercholesterolemia and atherosclerosis in murine models of hyperlipidemia

Arteriosclerosis, Thrombosis, and Vascular Biology

Volumn 31, Issue 5, 2011, Pages 1108-1115

  Ohshiro, Taichi ^a,b   Matsuda, Daisuke ^a   Sakai, Kent ^a   Degirolamo, Chiara ^c   Yagyu, Hiroaki ^b   Rudel, Lawrence L ^c   Omura, Satoshi ^a   Ishibashi, Shun ^b   Tomoda, Hiroshi ^a  

^a KITASATO UNIVERSITY   (Japan)

^b JICHI MEDICAL UNIVERSITY   (Japan)

^c WAKE FOREST SCHOOL OF MEDICINE   (United States)

Author keywords

atherosclerosis; hypercholesterolemia; inhibitors

Indexed keywords

ACYL COENZYME A CHOLESTEROL ACYLTRANSFERASE 2; APOLIPOPROTEIN E; CHOLESTEROL; CHOLESTEROL ACYLTRANSFERASE; CHOLESTEROL ACYLTRANSFERASE INHIBITOR; CHOLESTEROL ESTER; CHOLESTEROL LINOLEATE; CHOLESTEROL OLEATE; LOW DENSITY LIPOPROTEIN; PYRIPYROPENE A; UNCLASSIFIED DRUG; VERY LOW DENSITY LIPOPROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; AORTA; AORTA ATHEROSCLEROSIS; ARTICLE; ATHEROSCLEROTIC PLAQUE; CHOLESTEROL BLOOD LEVEL; CHOLESTEROL LIVER LEVEL; CHOLESTEROL METABOLISM; CHOLESTEROL SYNTHESIS; CONTROLLED STUDY; DRUG EFFICACY; DRUG INHIBITION; DRUG MEGADOSE; ENZYME ACTIVITY; ENZYME INHIBITION; HYPERCHOLESTEROLEMIA; HYPERLIPIDEMIA; IN VIVO STUDY; INTESTINE; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; TREATMENT OUTCOME;

ANALYSIS OF VARIANCE; ANIMALS; ANTICHOLESTEREMIC AGENTS; APOLIPOPROTEINS E; ATHEROSCLEROSIS; CHOLESTEROL ESTERS; CHOLESTEROL, DIETARY; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; ENZYME INHIBITORS; HYPERCHOLESTEROLEMIA; INTESTINAL ABSORPTION; INTESTINES; LIPOPROTEINS, LDL; LIPOPROTEINS, VLDL; LIVER; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; PYRIDINES; SESQUITERPENES; STEROL O-ACYLTRANSFERASE; TIME FACTORS;

EID: 79955602758     PISSN: 10795642     EISSN: None     Source Type: Journal    
DOI: 10.1161/ATVBAHA.111.223552     Document Type: Article

References (41)

1. Libby P. The forgotten majority: unfinished business in cardiovascular risk reduction. J Am Coll Cardiol. 2005;46:1225-1228. (Pubitemid 41615541)
2. Sliskovic DR, Picard JA, Krause BR. ACAT inhibitors: the search for a novel and effective treatment of hypercholesterolemia and atherosclerosis. Prog Med Chem. 2002;39:121-171.
3. Chang CC, Huh HY, Cadigan KM, Chang TY. 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. (Pubitemid 23292243)
4. Anderson RA, Joyce C, Davis M, Reagan JW, Clark M, Shelness GS, Rudel LL. Identification of a form of acyl-CoA:cholesterol acyltransferase specific to liver and intestine in nonhuman primates. J Biol Chem. 1998;273:26747-26754. (Pubitemid 28471691)
5. Cases S, Novak S, Zheng YW, Myers HM, Lear SR, Sande E, Welch CB, Lusis AJ, Spencer TA, Krause BR, Erickson SK, Farese RV Jr. ACAT-2, a second mammalian acyl-CoA:cholesterol acyltransferase: its cloning, expression, and characterization. J Biol Chem. 1998;273:26755-26764. (Pubitemid 28471692)
6. Oelkers P, Behari A, Cromley D, Billheimer JT, Sturley SL. Characterization of two human genes encoding acyl coenzyme A:cholesterol acyltransferase-related enzymes. J Biol Chem. 1998;273:26765-26771. (Pubitemid 28471693)
7. Parini P, Davis M, Lada AT, Erickson SK, Wright TL, Gustafsson U, Sahlin S, Einarsson C, Eriksson M, Angelin B, Tomoda H, Omura S, Willingham MC, Rudel LL. ACAT2 is localized to hepatocytes and is the major cholesterol-esterifying enzyme in human liver. Circulation. 2004; 110:2017-2023. (Pubitemid 39331916)
8. Accad M, Smith SJ, Newland DL, Sanan DA, King LE Jr, Linton MF, Fazio S, Farese RV Jr. Massive xanthomatosis and altered composition of atherosclerotic lesions in hyperlipidemic mice lacking acyl CoA:cholesterol acyltransferase 1. J Clin Invest. 2000;105:711-719. (Pubitemid 30164109)
9. Yagyu H, Kitamine T, Osuga J, Tozawa R, Chen Z, Kaji Y, Oka T, Perrey S, Tamura Y, Ohashi K, Okazaki H, Yahagi N, Shionoiri F, Iizuka Y, Harada K, Shimano H, Yamashita H, Gotoda T, Yamada N, Ishibashi S. 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. (Pubitemid 30481831)
10. Fazio S, Major AS, Swift LL, Gleaves LA, Accad M, Linton MF, Farese RV Jr. Increased atherosclerosis in LDL receptor-null mice lacking ACAT1 in macrophages. J Clin Invest. 2001;107:163-171. (Pubitemid 32096832)
11. Buhman KK, Accad M, Novak S, Choi RS, Wong JS, Hamilton RL, Turley S, Farese RV Jr. Resistance to diet-induced hypercholesterolemia and gallstone formation in ACAT2-deficient mice. Nat Med. 2000;6: 1341-1347. (Pubitemid 32001017)
12. Willner EL, Tow B, Buhman KK, Wilson M, Sanan DA, Rudel LL, Farese RV Jr. Deficiency of acyl CoA:cholesterol acyltransferase 2 prevents atherosclerosis in apolipoprotein E-deficient mice. Proc Natl Acad Sci USA. 2003;100:1262-1267. (Pubitemid 36183990)
13. Tardif JC, Gregoire J, L'Allier PL, Anderson TJ, Bertrand O, Reeves F, Title LM, Alfonso F, Schampaert E, Hassan A, McLain R, Pressler ML, Ibrahim R, Lesperance J, Blue J, Heinonen T, Rodes-Cabau J. Effects of the acyl coenzyme A:cholesterol acyltransferase inhibitor avasimibe on human atherosclerotic lesions. Circulation. 2004;110:3372-3377. (Pubitemid 39557502)
14. Nissen SE, Tuzcu EM, Brewer HB, Sipahi I, Nicholls SJ, Ganz P, Schoenhagen P, Waters DD, Pepine CJ, Crowe TD, Davidson MH, Deanfield JE, Wisniewski LM, Hanyok JJ, Kassalow LM. Effect of ACAT inhibition on the progression of coronary atherosclerosis. N Engl J Med. 2006;354:1253-1263.
15. Meuwese MC, de Groot E, Duivenvoorden R, Trip MD, Ose L, Maritz FJ, Basart DC, Kastelein JJ, Habib R, Davidson MH, Zwinderman AH, Schwocho LR, Stein EA. ACAT inhibition and progression of carotid atherosclerosis in patients with familial hypercholesterolemia: the CAPTIVATE randomized trial. JAMA. 2009;301:1131-1139.
16. Fazio S, Linton M. Failure of ACAT inhibition to retard atherosclerosis. N Engl J Med. 2006;354:1307-1309.
17. Dove DE, Su YR, Zhang W, Jerome WG, Swift LL, Linton MF, Fazio S. ACAT1 deficiency disrupts cholesterol efflux and alters cellular morphology in macrophages. Arterioscler Thromb Vasc Biol. 2005;25: 128-134. (Pubitemid 40054265)
18. Bell TA III, Brown JM, Graham MJ, Lemonidis KM, Crooke RM, Rudel LL. Liver-specific inhibition of acyl-coenzyme A:cholesterol acyltransferase 2 with antisense oligonucleotides limits atherosclerosis development in apolipoprotein B100-only low-density lipoprotein receptor/mice. Arterioscler Thromb Vasc Biol. 2006;26:1814-1820. (Pubitemid 44305335)
19. Tomoda H, Omura S. Potential therapeutics for obesity and atherosclerosis: inhibitors of neutral lipid metabolism from microorganisms. Pharmacol Ther. 2007;115:375-389. (Pubitemid 47362374)
20. Omura S, Tomoda H, Kim YK, Nishida H. Pyripyropenes, highly potent inhibitors of acyl-CoA:cholesterol acyltransferase produced by Aspergillus fumigatus. J Antibiot. 1993;46:1168-1169. (Pubitemid 23254161)
21. Tomoda H, Kim YK, Nishida H, Masuma R, Omura S. Pyripyropenes, novel inhibitors of acyl-CoA:cholesterol acyltransferase produced by Aspergillus fumigatus: I: production, isolation, and biological properties. J Antibiot. 1994;47:148-153. (Pubitemid 24075569)
22. Kim YK, Tomoda H, Nishida H, Sunazuka T, Obata R, Omura S. Pyripyropenes, novel inhibitors of acyl-CoA: cholesterol acyltransferase produced by Aspergillus fumigatus: II: structure elucidation of pyripyropenes A, B, C and D. J Antibiot. 1994;47:154-162. (Pubitemid 24075570)
23. Lada AT, Davis M, Kent C, Chapman J, Tomoda H, Omura S, Rudel LL. Identification of ACAT1-and ACAT2-specific inhibitors using a novel, cell-based fluorescence assay: individual ACAT uniqueness. J Lipid Res. 2004;45:378-386. (Pubitemid 38228836)
24. Ohshiro T, Rudel LL, Omura S, Tomoda H. Selectivity of microbial acyl-CoA: cholesterol acyltransferase inhibitors toward isozymes. J Antibiot. 2007;60:43-51.
25. Terasaka N, Miyazaki A, Kasanuki N, Ito K, Ubukata N, Koieyama T, Kitayama K, Tanimoto T, Maeda N, Inaba T. ACAT inhibitor pactimibe sulfate (CS-505) reduces and stabilizes atherosclerotic lesions by cholesterol-lowering and direct effects in apolipoprotein E-deficient mice. Atherosclerosis. 2007;190:239-247. (Pubitemid 46074038)
26. Ikenoya M, Yoshinaka Y, Kobayashi H, Kawamine K, Shibuya K, Sato F, Sawanobori K, Watanabe T, Miyazaki A. A selective ACAT-1 inhibitor, K-604, suppresses fatty streak lesions in fat-fed hamsters without affecting plasma cholesterol levels. Atherosclerosis. 2007;191:290-297. (Pubitemid 46400712)
27. Das A, Davis MA, Tomoda H, Omura S, Rudel LL. Identification of the interaction site within acyl-CoA:cholesterol acyltransferase 2 for the isoform-specific inhibitor pyripyropene A. J Biol Chem. 2008;283: 10453-10460.
28. Cho KH, An S, Lee WS, Paik YK, Kim YK, Jeong TS. Mass-production of human ACAT-1 and ACAT-2 to screen isoform-specific inhibitor: a different substrate specificity and inhibitory regulation. Biochem Biophys Res Commun. 2003;309:864-872. (Pubitemid 37122609)
29. Ohshiro T, Ohte S, Matsuda D, Ohtawa M, Nagamitsu T, Sunazuka T, Harigaya Y, Rudel LL, Omura S, Tomoda H. Selectivity of pyripyropene derivatives in inhibition toward acyl-CoA:cholesterol acyltransferase 2 isozyme. J Antibiot. 2008;61:503-508.
30. Rudel LL, Farese RV Jr. ACAT inhibition and the progression of coronary atherosclerosis. N Engl J Med. 2006;354:2616-2617; author reply 2616-2617. (Pubitemid 43882368)
31. Farese RV Jr. The nine lives of ACAT inhibitors. Arterioscler Thromb Vasc Biol. 2006;26:1684-1686. (Pubitemid 44305318)
32. Parini P, Eriksson M, Rudel LL. Carotid atherosclerosis progression and ACAT inhibition. JAMA. 2009;302:255; author reply 256-257.
33. Turley SD, Daggy BP, Dietschy JM. Psyllium augments the cholesterollowering action of cholestyramine in hamsters by enhancing sterol loss from the liver. Gastroenterology. 1994;107:444-452. (Pubitemid 24233319)
34. Veniant MM, Sullivan MA, Kim SK, Ambroziak P, Chu A, Wilson MD, Hellerstein MK, Rudel LL, Walzem RL, Young SG. Defining the atherogenicity of large and small lipoproteins containing apolipoprotein B100. J Clin Invest. 2000;106:1501-1510. (Pubitemid 32038588)
35. Bell TA III, Kelley K, Wilson MD, Sawyer JK, Rudel LL. Dietary fat-induced alterations in atherosclerosis are abolished by ACAT2-deficiency in ApoB100 only, LDLr/mice. Arterioscler Thromb Vasc Biol. 2007;27:1396-1402. (Pubitemid 46809431)
36. Lee RG, Willingham MC, Davis MA, Skinner KA, Rudel LL. Differential expression of ACAT1 and ACAT2 among cells within liver, intestine, kidney, and adrenal of nonhuman primates. J Lipid Res. 2000;41: 1991-2001. (Pubitemid 32038994)
37. Carr TP, Parks JS, Rudel LL. Hepatic ACAT activity in African green monkeys is highly correlated to plasma LDL cholesteryl ester enrichment and coronary artery atherosclerosis. Arterioscler Thromb. 1992;12: 1274-1283.
38. Warensjo E, Sundstrom J, Vessby B, Cederholm T, Riserus U. Markers of dietary fat quality and fatty acid desaturation as predictors of total and cardiovascular mortality: a population-based prospective study. Am J Clin Nutr. 2008;88:203-209. (Pubitemid 351988700)
39. Kashiwa M, Masuyama Y, Miyauchi H, Uchida T, Naganuma S, Kakuta H, Terada M, Kiriyama T, Matsuda K, Ito N, Iizumi Y, Takenaka T. Pharmacological properties of YM17E, an acyl-CoA:cholesterol acyltransferase inhibitor, and diarrheal effect in beagle dogs. Jpn J Pharmacol. 1997;73:41-50. (Pubitemid 27078009)
40. Trivedi BK, Purchase TS, Holmes A, Augelli-Szafran CE, Essenburg AD, Hamelehle KL, Stanfield RL, Bousley RF, Krause BR. Inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT): 7: development of a series of substituted N-phenyl-N-[(1-phenylcyclopentyl)methyl]ureas with enhanced hypocholesterolemic activity. J Med Chem. 1994;37: 1652-1659. (Pubitemid 24195480)
41. Namatame I, Tomoda H, Ishibashi S, Omura S. Antiatherogenic activity of fungal beauveriolides, inhibitors of lipid droplet accumulation in macrophages. Proc Natl Acad Sci USA. 2004;101:737-742. (Pubitemid 38121027)