Effects of the cholesteryl ester transfer protein inhibitor torcetrapib on VLDL apolipoprotein E metabolism

Journal of Lipid Research

Volumn 49, Issue 3, 2008, Pages 543-549

  Millar, John S ^a   Brousseau, Margaret E ^b   Diffenderfer, Margaret R ^b   Barrett, P Hugh R ^c   Welty, Francine K ^b,d   Cohn, Jeffrey S ^e   Wilson, Aisha ^a   Wolfe, Megan L ^a   Nartsupha, Chorthip ^b   Schaefer, Peter M ^b   Digenio, Andres G ^f   Mancuso, James P ^f   Dolnikowski, Gregory G ^b   Schaefer, Ernst J ^b   Rader, Daniel J ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b TUFTS UNIVERSITY   (United States)

^c UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^d BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

^e HEART RESEARCH INSTITUTE   (Australia)

^f PFIZER INC   (United States)

Author keywords

Lipoprotein kinetics; Low density lipoproteins; Triglyceride; Very low density lipoproteins

Indexed keywords

APOLIPOPROTEIN E; ATORVASTATIN; CHOLESTEROL ESTER TRANSFER PROTEIN INHIBITOR; LEUCINE; PLACEBO; TORCETRAPIB; VERY LOW DENSITY LIPOPROTEIN; CETP PROTEIN, HUMAN; CHOLESTEROL ESTER TRANSFER PROTEIN; ENZYME INHIBITOR; HEPTANOIC ACID DERIVATIVE; HYPOCHOLESTEROLEMIC AGENT; PYRROLE DERIVATIVE; QUINOLINE DERIVATIVE;

ADULT; AGED; ARTICLE; CIRCULATION; CLINICAL ARTICLE; CONTROLLED STUDY; DRUG EFFECT; DRUG MECHANISM; FEMALE; HUMAN; LIPOPROTEIN METABOLISM; LIPOPROTEIN SYNTHESIS; MALE; PRIORITY JOURNAL; PROTEIN DEGRADATION; BIOSYNTHESIS; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; DRUG ANTAGONISM; DRUG COMBINATION; KINETICS; METABOLISM; SINGLE BLIND PROCEDURE;

ANTICHOLESTEREMIC AGENTS; APOLIPOPROTEINS E; CHOLESTEROL ESTER TRANSFER PROTEINS; DRUG THERAPY, COMBINATION; ENZYME INHIBITORS; FEMALE; HEPTANOIC ACIDS; HUMANS; KINETICS; LIPOPROTEINS, VLDL; MALE; PYRROLES; QUINOLINES; SINGLE-BLIND METHOD;

EID: 42949138985     PISSN: 00222275     EISSN: 15397262     Source Type: Journal    
DOI: 10.1194/jlr.M700268-JLR200     Document Type: Article

References (24)

1. Brousseau, M. E., E. J. Schaefer, M. L. Wolfe, L. T. Bloedon, A. G. Digenio, R. W. Clark, J. P. Mancuso, and D. J. Rader. 2004. Effects of a potent inhibitor of cholesteryl ester transfer protein on plasma lipoproteins in subjects with low HDL cholesterol. N. Engl. J. Med. 350: 1505-1515.
2. Brousseau, M. E., M. R. Diffenderfer, J. S. Millar, C. Nartsupha, B. F. Asztalos, F. K. Welty, M. L. Wolfe, M. Rudling, I. Bjorkhem, 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.
3. Millar, J. S., M. L. Wolfe, A. Faruqi, M. E. Brousseau, M. R. Diffenderfer, C. Nartsupha, F. K. Welty, S. E. Panagotopulos, A. G. Digenio, E. J. Schaefer, et al. 2006. Effects of torcetrapib, a cholesteryl ester transfer protein inhibitor, on apolipoprotein B100 metabolism. Arterioscler. Thromb. Vasc. Biol. 26: 1350-1356.
4. Blum, C. B., L. Aron, and R. Sciacca. 1980. Radioimmunoassay studies of human apolipoprotein E. J. Clin. Invest. 66: 1240-1250.
5. Gregg, R. E., and H. B. Brewer, Jr. 1988. The role of apolipoprotein E and lipoprotein receptors in modulating the in vivo metabolism of apolipoprotein B-containing lipoproteins in humans. Clin. Chem. 34: B28-B32.
6. Millar, J. S., A. H. Lichtenstein, J. M. Ordovas, G. G. Dolnikowski, and E. J. Schaefer. 2001. Human triglyceride-rich lipoprotein apoE kinetics and its relationship to LDL apo B-100 metabolism. Atherosclerosis. 155: 477-485.
7. Cohn, J. S., M. Tremblay, M. Amiot, D. Bouthillier, M. Roy, J. Genest, Jr., and J. Davignon. 1996. Plasma concentration of apolipoprotein E in intermediate-sized remnant-like lipoproteins in normolipidemic and hyperlipidemic subjects. Arterioscler. Thromb. Vasc. Biol. 16: 149-159.
8. Cohn, J. S., D. A. Wagner, S. D. Cohn, J. S. Millar, and E. J. Schaefer. 1990. Measurement of very low density and low density lipoprotein apolipoprotein (apo) B-100 and high density lipoprotein apo A-I production in human subjects using deuterated leucine. Effect of fasting and feeding. J. Clin. Invest. 85: 804-811.
9. Tan, C. E., E. S. Tai, C. S. Tan, K. S. Chia, J. Lee, S. K. Chew, and J. M. Ordovas. 2003. APOE polymorphism and lipid profile in three ethnic groups in the Singapore population. Atherosclerosis. 170: 253-260.
10. Adams, R. F., F. L. Vandemark, and G. J. Schmidt. 1977. Ultramicro GC determination of amino acids using glass open tubular columns and a nitrogen-selective detector. J. Chromatogr. Sci. 15: 63-68.
11. Cohn, J. S., E. J. Johnson, J. S. Millar, S. D. Cohn, R. W. Milne, Y. L. Marcel, R. M. Russell, and E. J. Schaefer. 1993. Contribution of apoB-48 and apoB-100 triglyceride-rich lipoproteins (TRL) to postprandial increases in the plasma concentration of TRL triglycerides and retinyl esters. J. Lipid Res. 34: 2033-2040.
12. Welty, F. K., A. H. Lichtenstein, P. H. Barrett, J. L. Jenner, G. G. Dolnikowski, and E. J. Schaefer. 2000. Effects of apoE genotype on apoB-48 and apoB-100 kinetics with stable isotopes in humans. Arterioscler. Thromb. Vasc. Biol. 20: 1807-1810.
13. de Grooth, G. J., J. A. Kuivenhoven, A. F. H. Stalenhoef, J. de Graaf, A. H. Zwinderman, J. L. Posma, A. van Tol, and J. J. P. Kastelein. 2002. Efficacy and safety of a novel cholesteryl ester transfer protein inhibitor, JTT-705, in humans: a randomized phase II dose-response study. Circulation. 105: 2159-2165.
14. 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.
15. Tanne, J. H. 2006. Pfizer stops clinical trials of heart drug. BMJ. 333: 1237.
16. Hatters, D. M., M. S. Budamagunta, J. C. Voss, and K. H. Weisgraber. 2005. Modulation of apolipoprotein E structure by domain interaction: differences in lipid-bound and lipid-free forms. J. Biol. Chem. 280: 34288-34295.
17. Fisher, R. M., S. W. Coppack, S. M. Humphreys, G. F. Gibbons, and K. N. Frayn. 1995. Human triacylglycerol-rich lipoprotein subfractions as substrates for lipoprotein lipase. Clin. Chim. Acta. 236: 7-17.
18. Le, N. A., J. C. Gibson, and H. N. Ginsberg. 1988. Independent regulation of plasma apolipoprotein C-II and C-III concentrations in very low density and high density lipoproteins: implications for the regulation of the catabolism of these lipoproteins. J. Lipid Res. 29: 669-677.
19. Campos, H., D. Perlov, C. Khoo, and F. M. Sacks. 2001. Distinct patterns of lipoproteins with apoB defined by presence of apoE or apoC-III in hypercholesterolemia and hypertriglyceridemia. J. Lipid Res. 42: 1239-1249.
20. Qu, S., G. Perdomo, D. Su, F. M. D'Souza, N. S. Shachter, and H. H. Dong. 2007. Effects of apoA-V on HDL and VLDL metabolism in APOC3 transgenic mice. J. Lipid Res. 48: 1476-1487.
21. Hennessy, L. K., J. Osada, J. M. Ordovas, R. J. Nicolosi, A. F. Stucchi, M. E. Brousseau, and E. J. Schaefer. 1992. Effects of dietary fats and cholesterol on liver lipid content and hepatic apolipoprotein A-I, B, and E and LDL receptor mRNA levels in cebus monkeys. J. Lipid Res. 33: 351-360.
22. Cohn, J. S., M. Tremblay, R. Batal, H. Jacques, L. Veilleux, C. Rodriguez, P. H. Barrett, D. Dubreuil, M. Roy, L. Bernier, et al. 2002. Effect of atorvastatin on plasma apoE metabolism in subjects with combined hyperlipidemia. J. Lipid Res. 43: 1464-1471.
23. Davignon, J., R. E. Gregg, and C. F. Sing. 1988. Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis. 8: 1-21.
24. Zheng, C., C. Khoo, K. Ikewaki, and F. M. Sacks. 2007. Rapid turnover of apolipoprotein C-III-containing triglyceride-rich lipoproteins contributing to the formation of LDL subfractions. J. Lipid Res. 48: 1190-1203.