Modulating cholesteryl ester transfer protein activity maintains efficient pre-β-HDL formation and increases reverse cholesterol transport

Journal of Lipid Research

Volumn 51, Issue 12, 2010, Pages 3443-3454

  Niesor, Eric J ^a   Magg, Christine ^a,c   Ogawa, Naoto ^b   Okamoto, Hiroshi ^b   Von Der Mark, Elisabeth ^a   Matile, Hugues ^a   Schmid, Georg ^a   Clerc, Roger G ^a   Chaput, Evelyne ^a   Blum Kaelin, Denise ^a   Huber, Walter ^a   Thoma, Ralf ^a   Pflieger, Philippe ^a   Kakutani, Makoto ^b   Takahashi, Daisuke ^b   Dernick, Gregor ^a   Maugeais, Cyrille ^a  

^a F HOFFMANN LA ROCHE LTD   (Switzerland)

^b JAPAN TOBACCO INC   (Japan)

^c CYTOS BIOTECHNOLOGY AG   (Switzerland)

Author keywords

Anacetrapib; Apolipoproteins; Bile acids and salts metabolism; CETP; Dalcetrapib; High density lipoprotein functionality; Lipoproteins metabolism; Torcetrapib

Indexed keywords

ANACETRAPIB; BILE ACID; CHOLESTEROL ESTER; CHOLESTEROL ESTER TRANSFER PROTEIN; CHOLESTEROL ESTER TRANSFER PROTEIN INHIBITOR; CYSTEINE; DALCETRAPIB; HIGH DENSITY LIPOPROTEIN; HIGH DENSITY LIPOPROTEIN 2; HIGH DENSITY LIPOPROTEIN 3; HYPOCHOLESTEROLEMIC AGENT; PRE BETA HIGH DENSITY LIPOPROTEIN; STEROL; TORCETRAPIB; TRITIUM; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CHOLESTEROL TRANSPORT; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; DRUG MECHANISM; HUMAN; HUMAN TISSUE; IN VITRO STUDY; IN VIVO STUDY; LIPOPROTEIN METABOLISM; LIPOPROTEIN SYNTHESIS; MACROPHAGE; MALE; NONHUMAN; PLASMA; PRIORITY JOURNAL; REVERSE CHOLESTEROL TRANSPORT; SYRIAN HAMSTER;

ANIMALS; ANTICHOLESTEREMIC AGENTS; BILE ACIDS AND SALTS; BINDING SITES; BIOLOGICAL TRANSPORT; CHOLESTEROL; CHOLESTEROL ESTER TRANSFER PROTEINS; CRICETINAE; DOSE-RESPONSE RELATIONSHIP, DRUG; ENZYME-LINKED IMMUNOSORBENT ASSAY; HIGH-DENSITY LIPOPROTEINS, PRE-BETA; HUMANS; OXAZOLIDINONES; QUINOLINES; SULFHYDRYL COMPOUNDS;

EID: 78650054881     PISSN: 00222275     EISSN: 15397262     Source Type: Journal    
DOI: 10.1194/jlr.M008706     Document Type: Article

References (55)

1. Gordon, T., W. P. Castelli, M. C. Hjortland, W. B. Kannel, and T. R. Dawber. 1977. High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am. J. Med. 62: 707-714.
2. Neeli, H., and D. J. Rader. 2008. Cholesteryl ester transfer protein (CETP) inhibitors: is there life after torcetrapib? Cardiol. Clin. 26: 537-546.
3. Clark, R. W., T. A. Sutfin, R. B. Ruggeri, A. T. Willauer, E. D. Sugarman, G. Magnus-Aryitey, P. G. Cosgrove, T. M. Sand, R. T. Wester, J. A. Williams, et al. 2004. Raising high-density lipoprotein in humans through inhibition of cholesteryl ester transfer protein: an initial multidose study of torcetrapib. Arterioscler. Thromb. Vasc. Biol. 24: 490-497.
4. Krishna, R., A. J. Bergman, B. Jin, M. Fallon, J. Cote, P. Van Hoydonck, T. Laethem, I. N. Gendrano III, K. Van Dyck, D. Hilliard, et al. 2008. Multiple-dose pharmacodynamics and pharmacokinetics of anacetrapib, a potent cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects. Clin. Pharmacol. Ther. 84: 679-683.
5. Barter, P. J., M. Caulfield, M. Eriksson, S. M. Grundy, J. J. Kastelein, M. Komajda, J. Lopez-Sendon, L. Mosca, J. C. Tardif, D. D. Waters, et al. 2007. Effects of torcetrapib in patients at high risk for coronary events. N. Engl. J. Med. 357: 2109-2122.
6. Hu, X., J. D. Dietz, C. Xia, D. R. Knight, W. T. Loging, A. H. Smith, H. Yuan, D. A. Perry, and J. Keiser. 2009. Torcetrapib induces aldosterone and cortisol production by an intracellular calcium-mediated mechanism independently of cholesteryl ester transfer protein inhibition. Endocrinology. 150: 2211-2219.
7. Stroes, E. S. G., J. J. P. Kastelein, A. Bernardeau, O. Kuhlmann, D. Blum, L. A. Campos, R. G. Clerc, and E. J. Niesor. 2009. Dalcetrapib: no off-target toxicity on blood pressure or renin-angiotensin aldosterone system-related genes in rats. Br. J. Pharmacol. 158: 1763-1770.
8. Forrest, M. J., D. Bloomfield, R. J. Briscoe, P. N. Brown, A. M. Cumiskey, J. Ehrhart, J. C. Hershey, W. J. Keller, X. Ma, H. E. McPherson, et al. 2008. Torcetrapib-induced blood pressure elevation is independent of CETP inhibition and is accompanied by increased circulating levels of aldosterone. Br. J. Pharmacol. 154: 1465-1473.
9. Okamoto, H., F. Yonemori, K. Wakitani, T. Minowa, K. Maeda, and H. Shinkai. 2000. A cholesteryl ester transfer protein inhibitor attenuates atherosclerosis in rabbits. Nature. 406: 203-207.
10. Shinkai, H. 2009. Cholesteryl ester transfer protein inhibitors as high-density lipoprotein raising agents. Expert Opin. Ther. Pat. 19: 1229-1237.
11. Connolly, D. T., D. Heuvelman, and K. Glenn. 1996. Inactivation of cholesteryl ester transfer protein by cysteine modification. Biochem. Biophys. Res. Commun. 223: 42-47.
12. Stein, E. A., E. S. Stroes, G. Steiner, B. M. Buckley, A. M. Capponi, T. Burgess, E. J. Niesor, D. Kallend, and J. J. Kastelein. 2009. Safety and tolerability of dalcetrapib. Am. J. Cardiol. 104: 82-91.
13. Schwartz, G.G., A.G. Olsson, C.M. Ballantyne, P.J. Barter, I.M. Holme, D. Kallend, L.A. Leiter, E. Leitersdorf, J.J.V. McMurray, P.K. Shah, et al. 2009. Rationale and design of the dal-OUTCOMES trial: efficacy and safety of dalcetrapib in patients with recent acute coronary syndrome. Am. Heart J. 158: 896-901.
14. Clark, R. W., R. B. Ruggeri, D. Cunningham, and M. J. Bamberger. 2006. Description of the torcetrapib series of cholesteryl ester transfer protein inhibitors, including mechanism of action. J. Lipid Res. 47: 537-552.
15. Swenson, T. L., C. B. Hesler, M. L. Brown, E. Quinet, P. P. Trotta, M. F. Haslanger, F. C. Gaeta, Y. L. Marcel, R. W. Milne, and A. R. Tall. 1989. Mechanism of cholesteryl ester transfer protein inhibition by a neutralizing monoclonal antibody and mapping of the monoclonal antibody epitope. J. Biol. Chem. 264: 14318-14326.
16. Qiu, X., A. Mistry, M. J. Ammirati, B. A. Chrunyk, R. W. Clark, Y. Cong, J. S. Culp, D. E. Danley, T. B. Freeman, K. F. Geoghegan, et al. 2007. Crystal structure of cholesteryl ester transfer protein reveals a long tunnel and four bound lipid molecules. Nat. Struct. Mol. Biol. 14: 106-113.
17. Kunitake, S. T., C. M. Mendel, and L. K. Hennessy. 1992. Interconversion between apolipoprotein A-I-containing lipoproteins of pre-beta and alpha electrophoretic mobilities. J. Lipid Res. 33: 1807-1816.
18. Rye, K. A., and P. J. Barter. 2004. Formation and metabolism of prebeta-migrating, lipid-poor apolipoprotein A-I. Arterioscler. Thromb. Vasc. Biol. 24: 421-428.
19. Ha, Y. C., L. Gorjatschko, and P. J. Barter. 1983. Changes in the density distribution of pig high density lipoproteins during incubation in vitro. Influence of esterified cholesterol transfer activity. Atherosclerosis. 48: 253-263.
20. Paromov, V. M., and R. E. Morton. 2003. Lipid transfer inhibitor protein defines the participation of high-density lipoprotein subfractions in lipid transfer reactions mediated by cholesterol ester transfer protein (CETP). J. Biol. Chem. 278: 40859-40866.
21. Sacks, F. M., L. L. Rudel, A. Conner, H. Akeefe, G. Kostner, T. Baki, G. Rothblat, M. de la Llera-Moya, B. Asztalos, T. Perlman, et al. 2009. Selective delipidation of plasma HDL enhances reverse cholesterol transport in vivo. J. Lipid Res. 50: 894-907.
22. Tall, A. R., L. Yvan-Charvet, N. Terasaka, T. Pagler, and N. Wang. 2008. HDL, ABC transporters, and cholesterol efflux: implications for the treatment of atherosclerosis. Cell Metab. 7: 365-375.
23. Collet, X., A. R. Tall, H. Serajuddin, K. Guendouzi, L. Royer, H. Oliveira, R. Barbaras, X. C. Jiang, and O. L. Francone. 1999. Remodeling of HDL by CETP in vivo and by CETP and hepatic lipase in vitro results in enhanced uptake of HDL CE by cells expressing scavenger receptor B-I. J. Lipid Res. 40: 1185-1193.
24. Tanigawa, H., J. T. Billheimer, J. Tohyama, Y. Zhang, G. Rothblat, and D. J. Rader. 2007. Expression of cholesteryl ester transfer protein in mice promotes macrophage reverse cholesterol transport. Circulation. 116: 1267-1273.
25. Brousseau, M. E., M. R. Diffenderfer, J. S. Millar, C. Nartsupha, B. F. Asztalos, F. K. Welty, M. L. Wolfe, M. Rudling, I. Björkhem, B. Angelin, et al. 2005. Effects of cholesteryl ester transfer protein inhibition on high-density lipoprotein subspecies, apolipoprotein A-I metabolism, and fecal sterol excretion. Arterioscler. Thromb. Vasc. Biol. 25: 1057-1064.
26. Rader, D. J., E. T. Alexander, G. L. Weibel, J. Billheimer, and G. H. Rothblat. 2009. The role of reverse cholesterol transport in animals and humans and relationship to atherosclerosis. J. Lipid Res. 50 (Suppl.): 189-194.
27. Tchoua, U., W. D'Souza, N. Mukhamedova, D. Blum, E. Niesor, J. Mizrahi, C. Maugeais, and D. Sviridov. 2008. The effect of cholesteryl ester transfer protein overexpression and inhibition on reverse cholesterol transport. Cardiovasc. Res. 77: 732-739.
28. Roy, P., R. MacKenzie, T. Hirama, X-C. Jiang, P. Kussie, A. Tall, E. Rassart, and R. Milne. 1996. Structure-function relationships of human cholesteryl ester transfer protein: analysis using monoclonal antibodies. J. Lipid Res. 37: 22-34.
29. Tollefson, J. H., and J. J. Albers. 1986. Isolation, characterization, and assay of plasma lipid transfer proteins. Methods Enzymol. 129: 797-816.
30. Connolly, D. T., B. J. Witherbee, M. A. Melton, R. C. Durley, M. L. Grapperhaus, B. R. McKinnis, W. F. Vernier, M. A. Babler, J. J. Shieh, M. E. Smith, et al. 2000. Stereospecific inhibition of CETP by chiral N,N-disubstituted trifluoro-3-amino-2-propanols. Biochemistry. 39: 13870-13879.
31. Weinberg, R. B., V. R. Cook, J. B. Jones, P. Kussie, and A. R. Tall. 1994. Interfacial properties of recombinant human cholesterol ester transfer protein. J. Biol. Chem. 269: 29588-29591.
32. Ohnishi, T., S. Yokoyama, and A. Yamamoto. 1990. Rapid purification of human plasma lipid transfer proteins. J. Lipid Res. 31: 397-406.
33. Davis, H. L., R. Weeratna, T. J. Waldschmidt, L. Tygrett, J. Schorr, and A. M. Krieg. 1998. CpG DNA is a potent enhancer of specific immunity in mice immunized with recombinant hepatitis B surface antigen. J. Immunol. 160: 870-876.
34. Köhler, G., and C. Milstein. 1975. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 256: 495-497.
35. Takahashi, H., A. Takahashi, M. Maki, H. Sasai, and M. Kamada. 2001. Effect of CETP on the plasma lipoprotein profile in four strains of transgenic mouse. Biochem. Biophys. Res. Commun. 283: 118-123.
36. Derks, M., S. Fowler, and O. Kuhlmann. 2009. A single-center, open-label, one-sequence study of dalcetrapib coadministered with ketoconazole, and an in vitro study of the S-methyl metabolite of dalcetrapib. Clin. Ther. 31: 586-599
37. Miida, T., O. Miyazaki, Y. Nakamura, S. Hirayama, O. Hanyu, I. Fukamachi, and M. Okada. 2003. Analytical performance of a sandwich enzyme immunoassay for pre beta 1-HDL in stabilized plasma. J. Lipid Res. 44: 645-650.
38. Kleinman, Y., G. Halperin, O. Stein, and Y. Stein. 1982. Long-lived labeling of phagocytic cells with analogs of atheroma lipids. Atherosclerosis. 43: 1-6.
39. Folch, J., M. Lees, and G. H. Sloane Stanley. 1957. A simple method for the isolation and purification of total lipids from animal tissues. J. Biol. Chem. 226: 497-509.
40. Naik, S. U., X. Wang, J. S. Da Silva, M. Jaye, C. H. Macphee, M. P. Reilly, J. T. Billheimer, G. H. Rothblat, and D. J. Rader. 2006. Pharmacological activation of liver X receptors promotes reverse cholesterol transport in vivo. Circulation. 113: 90-97.
41. Epps, D. E., and A. F. Vosters. 2002. The essential role of a free sulfhydryl group in blocking the cholesteryl site of cholesteryl ester transfer protein (CETP). Chem. Phys. Lipids. 114: 113-122.
42. Hope, H. R., D. Heuvelman, K. Duffin, C. Smith, J. Zablocki, R. Schilling, S. Hegde, L. Lee, B. Witherbee, M. Baganoff, et al. 2000. Inhibition of cholesteryl ester transfer protein by substituted dithiobisnicotinic acid dimethyl ester: involvement of a critical cysteine. J. Lipid Res. 41: 1604-1614.
43. Ranalletta, M., K. K. Bierilo, Y. Chen, D. Milot, Q. Chen, E. Tung, C. Houde, N. H. Elowe, M. Garcia-Calvo, G. Porter, et al. 2010. Biochemical characterization of cholesteryl ester transfer protein inhibitors. J. Lipid Res. 51: 2739-2752.
44. Bruce, C., L. J. Beamer, and A. R. Tall. 1998. The implications of the structure of the bactericidal/permeability-increasing protein on the lipid-transfer function of the cholesteryl ester transfer protein. Curr. Opin. Struct. Biol. 8: 426-434.
45. Connolly, D. T., J. McIntyre, D. Heuvelman, E. E. Remsen, R. E. McKinnie, L. Vu, M. Melton, R. Monsell, E. S. Krul, and K. Glenn. 1996. Physical and kinetic characterization of recombinant human cholesteryl ester transfer protein. Biochem. J. 390: 39-47.
46. Cunningham, D., W. Lin, L. R. Hoth, D. E. Danley, R. B. Ruggeri, K. F. Geoghegan, B. A. Chrunyk, and J. G. Boyd. 2008. Biophysical and biochemical approach to locating an inhibitor binding site on cholesteryl ester transfer protein. Bioconjug. Chem. 19: 1604-1613.
47. Kotake, H., L. B. Agellon, and S. Yokoyama. 1997. Modification of the N-terminal cysteine of plasma cholesteryl ester transfer protein selectively inhibits triglyceride transfer activity. Biochim. Biophys. Acta. 1347: 69-74.
48. Barter, P. J. 2002. Hugh Sinclair lecture: the regulation and remodelling of HDL by plasma factors. Atheroscler. Suppl. 3: 39-47.
49. Lagrost, L., P. Gambert, V. Dangremont, A. Athias, and C. Lallemant. 1990. Role of cholesteryl ester transfer protein (CETP) in the HDL conversion process as evidenced by using anti-CETP monoclonal antibodies. J. Lipid Res. 31: 1569-1575. (Pubitemid 20321718)
50. Rye, K. A., M. Jauhiainen, P. J. Barter, and C. Ehnholm. 1998. Triglyceride-enrichment of high density lipoproteins enhances their remodelling by phospholipid transfer protein. J. Lipid Res. 39: 613-622.
51. Morton, R. E., and D. J. Greene. 1994. Regulation of lipid transfer between lipoproteins by an endogenous plasma protein: selective inhibition among lipoprotein classes. J. Lipid Res. 35: 836-847.
52. Zhang, Y., I. Zanotti, M. P. Reilly, J. M. Glick, G. H. Rothblat, and D. J. Rader. 2003. Overexpression of apolipoprotein A-I promotes reverse transport of cholesterol from macrophages to feces in vivo. Circulation. 108: 661-663.
53. Zuckerman, S. H., and G. F. Evans. 1995. Cholesteryl ester transfer protein inhibition in hypercholesterolemic hamsters: kinetics of apoprotein changes. Lipids. 30: 307-311.
54. Schwartz, C. C., L. G. Halloran, Z. R. Vlahcevic, D. H. Gregory, and L. Swell. 1978. Preferential utilization of free cholesterol from high-density lipoproteins for biliary cholesterol secretion in man. Science. 200: 62-64.
55. Nanjee, M. N., C. J. Cooke, R. Garvin, F. Semeria, G. Lewis, W. L. Olszewski, and N. E. Miller. 2001. Intravenous apoA-I/lecithin discs increase pre-β-HDL concentration in tissue fluid and stimulate reverse cholesterol transport in humans. J. Lipid Res. 42: 1586-1593.