Effects of the cholesteryl ester transfer protein inhibitor torcetrapib on apolipoprotein B100 metabolism in humans

Arteriosclerosis, Thrombosis, and Vascular Biology

Volumn 26, Issue 6, 2006, Pages 1350-1356

  Millar, John S ^a,f   Brousseau, Margaret E ^b   Diffenderfer, Margaret R ^b   Barrett, P Hugh R ^c   Welty, Francine K ^b,d   Faruqi, Aisha ^a   Wolfe, Megan L ^a   Nartsupha, Chorthip ^b   Digenio, Andres G ^e   Mancuso, James P ^e   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 PFIZER INC   (United States)

^f JM USDA HNRCA at Tufts University ^*  (United States)

Author keywords

CETP inhibition; Cholesteryl ester transfer protein; Lipoprotein kinetics; Low density lipoproteins; Triglyceride; Very low density lipoproteins

Indexed keywords

APOLIPOPROTEIN B; APOLIPOPROTEIN B100; ATORVASTATIN; CHOLESTEROL ESTER TRANSFER PROTEIN; CHOLESTEROL ESTER TRANSFER PROTEIN INHIBITOR; INTERMEDIATE DENSITY LIPOPROTEIN; LEUCINE; LIPOPROTEIN; LOW DENSITY LIPOPROTEIN; PLACEBO; TORCETRAPIB; VERY LOW DENSITY LIPOPROTEIN; CARRIER PROTEIN; CETP PROTEIN, HUMAN; GLYCOPROTEIN; HEPTANOIC ACID DERIVATIVE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LIPID; PYRROLE DERIVATIVE; QUINOLINE DERIVATIVE;

ADULT; AGED; ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CROSSOVER PROCEDURE; DRUG EFFECT; DRUG MECHANISM; HUMAN; KINETICS; PRIORITY JOURNAL; PROTEIN METABOLISM; BIOSYNTHESIS; BLOOD; DRUG ANTAGONISM; DRUG POTENTIATION; METABOLISM; MIDDLE AGED; SINGLE BLIND PROCEDURE;

ADULT; AGED; APOLIPOPROTEIN B-100; APOLIPOPROTEINS B; CARRIER PROTEINS; CHOLESTEROL ESTER TRANSFER PROTEINS; CROSS-OVER STUDIES; DRUG SYNERGISM; GLYCOPROTEINS; HEPTANOIC ACIDS; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; KINETICS; LIPIDS; LIPOPROTEINS; LIPOPROTEINS, IDL; LIPOPROTEINS, LDL; LIPOPROTEINS, VLDL; MIDDLE AGED; PYRROLES; QUINOLINES; SINGLE-BLIND METHOD;

EID: 33644839739     PISSN: 10795642     EISSN: None     Source Type: Journal    
DOI: 10.1161/01.ATV.0000219695.84644.56     Document Type: Article

References (26)

1. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). J Am Med Assoc. 2001;285:2486-2497.
2. Barter PJ, Brewer HB Jr, Chapman MJ, Hennekens CH, Rader DJ, Tall AR. Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis. Arterioscler Thromb Vasc Biol. 2003;23:160-167.
3. Agellon LB, Walsh A, Hayek T, Moulin P, Jiang XC, Shelanski SA, Breslow JL, Tall AR. Reduced high density lipoprotein cholesterol in human cholesteryl ester transfer protein transgenic mice. J Biol Chem. 1991;266:10796-10801.
4. Gaynor BJ, Sand T, Clark RW, Aiello RJ, Bamberger MJ, Moberly JB. Inhibition of cholesteryl ester transfer protein activity in hamsters alters HDL lipid composition. Atherosclerosis. 1994;110:101-109.
5. Okamoto H, Yonemori F, Wakitani K, Minowa T, Maeda K, Shinkai H. A cholesteryl ester transfer protein inhibitor attenuates atherosclerosis in rabbits. Nature. 2000;406:203-207.
6. de Grooth GJ, Kuivenhoven JA, Stalenhoef AFH, de Graaf J, Zwinderman AH, Posma JL, van Tol A, Kastelein JJP. Efficacy and safety of a novel cholesteryl ester transfer protein inhibitor, JTT-705, in humans: a randomized phase II dose-response study. Circulation. 2002;105:2159-2165.
7. Clark RW, Sutfin TA, Ruggeri RB, Willauer AT, Sugarman ED, Magnus-Aryitey G, Cosgrove PG, Sand TM, Wester RT, Williams JA, Perlman ME, Bamberger MJ. Raising high-density lipoprotein in humans through inhibition of cholesteryl ester transfer protein: an initial multidose study of torcetrapib. Arterioscler Thromb Vasc Biol. 2004;24:490-497.
8. Brousseau ME, Schaefer EJ, Wolfe ML, Bloedon LT, Digenio AG, Clark RW, Mancuso JP, Rader DJ. Effects of a potent inhibitor of cholesteryl ester transfer protein on plasma lipoproteins in subjects with low HDL cholesterol. N Engl J Med. 2004;350:1505-1515.
9. Brousseau ME, Diffenderfer MR, Millar JS, Nartsupha C, Asztalos BF, Welty FK, Wolfe ML, Rudling M, Bjorkhem I, Angelin B, Mancuso JP, Digenio AG, Rader DJ, Schaefer EJ. Effects of cholesteryl ester transfer protein inhibition on high-density lipoprotein subspecies, apolipoprotein A-I metabolism, and fecal sterol excretion. Arterioscler Thromb Vasc Biol. 2005;25:1057-1064.
10. Cohn JS, Wagner DA, Cohn SD, Millar JS, Schaefer EJ. 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. 1990;85:804-811.
11. Warnick GR, Benderson J, Albers JJ. Dextran sulfate-Mg2+ precipitation procedure for quantitation of high-density lipoprotein cholesterol. Clin Chem. 1982;28:1379-1388.
12. McNamara JR, Schaefer EJ. Automated enzymatic standardized lipid analyses for plasma and lipoprotein fractions. Clin Chim Acta. 1987;166:1-8.
13. Ordovas JM, Peterson JP, Santaniello P, Cohn JS, Wilson PW, Schaefer EJ. Enzyme-linked immunosorbent assay for human plasma apolipoprotein B. J Lipid Res. 1987;28:1216-1224.
14. Cohn JS, McNamara JR, Cohn SD, Ordovas JM, Schaefer EJ. Plasma apolipoprotein changes in the triglyceride-rich lipoprotein fraction of human subjects fed a fat-rich meal. J Lipid Res. 1988;29:925-936.
15. Millar JS, Lichtenstein AH, Cuchel M, Dolnikowski GG, Hachey DL, Cohn JS, Schaefer EJ. Impact of age on the metabolism of VLDL, IDL, and LDL apolipoprotein B-100 in men. J Lipid Res. 1995;36:1155-1167.
16. Parhofer KG, Barrett PHR, Bier D, Schonfeld G. Determination of kinetic parameters of apolipoprotein B metabolism using amino acids labeled with stable isotopes. J Lipid Res. 1991;8:1311-1323.
17. Jiang XC, Masucci-Magoulas L, Mar J, Lin M, Walsh A, Breslow JL, Tall A. Down-regulation of mRNA for the low density lipoprotein receptor in transgenic mice containing the gene for human cholesteryl ester transfer protein. Mechanism to explain accumulation of lipoprotein B particles. J Biol Chem. 1993;268:27406-27412.
18. Liu J, Zhang YL, Spence MJ, Vestal RE, Wallace PM, Grass DS. Liver LDL receptor mRNA expression is decreased in human ApoB/CETP double transgenic mice and is regulated by diet as well as the cytokine oncostatin M. Arterioscler Thromb Vasc Biol. 1997;17:2948-2954.
19. Ikewaki K, Nishiwaki M, Sakamoto T, Ishikawa T, Fairwell T, Zech LA, Nagano M, Nakamura H, Brewer HB Jr, Rader DJ. Increased catabolic rate of low density lipoproteins in humans with cholesteryl ester transfer protein deficiency. J Clin Invest. 1995;96:1573-1581.
20. Millar JS, Maugeais C, Ikewaki K, Kolansky DM, Barrett PH, Budreck EC, Boston RC, Tada N, Mochizuki S, Defesche JC, Wilson JM, Rader DJ. Complete deficiency of the low-density lipoprotein receptor is associated with increased apolipoprotein B-100 production. Arterioscler Thromb Vasc Biol. 2005;25:560-565.
21. Millar JS, Lichtenstein AH, Ordovas JM, Dolnikowski GG, Schaefer EJ. Human triglyceride-rich lipoprotein apo E kinetics and its relationship to LDL apo B-100 metabolism. Atherosclerosis. 2001;155:477-485.
22. Forster LF, Stewart G, Bedford D, Stewart JP, Rogers E, Shepherd J, Packard CJ, Caslake MJ. Influence of atorvastatin and simvastatin on apolipoprotein B metabolism in moderate combined hyperlipidemic subjects with low VLDL and LDL fractional clearance rates. Atherosclerosis. 2002;164:129-145.
23. Cuchel M, Schaefer EJ, Millar JS, Jones PJ, Dolnikowski GG, Vergani C, Lichtenstein AH. Lovastatin decreases de novo cholesterol synthesis and LDL Apo B-100 production rates in combined-hyperlipidemic males. Arterioscler Thromb Vasc Biol. 1997;17:1910-1917.
24. Berglund L, Witztum JL, Galeano NF, Khouw AS, Ginsberg HN, Ramakrishnan R. Three-fold effect of lovastatin treatment on low density lipoprotein metabolism in subjects with hyperlipidemia: increase in receptor activity, decrease in apoB production, and decrease in particle affinity for the receptor. Results from a novel triple-tracer approach. J Lipid Res. 1998;39:913-924.
25. Guerin M, Egger P, Soudant C, Le Goff W, van Tol A, Dupuis R, Chapman MJ. Dose-dependent action of atorvastatin in type IIB hyperlipidemia: preferential and progressive reduction of atherogenic apoB containing lipoprotein subclasses (VLDL-2, IDL, small dense LDL) and stimulation of cellular cholesterol efflux. Atherosclerosis. 2002;163:287-296.
26. Berneis KK, Krauss RM. Metabolic origins and clinical significance of LDL heterogeneity. J Lipid Res. 2002;43:1363-1379.