Effect of cholesteryl ester transfer protein inhibitor on vitamin E transport should be studied
Refers to article:
Efficacy and safety of the cholesteryl ester transfer protein inhibitor anacetrapib as monotherapy and coadministered with atorvastatin in dyslipidemic patients
, 22 December 2008
Daniel Bloomfield, Gary L. Carlson, Aditi Sapre, Diane Tribble, James M. McKenney, Thomas W. Littlejohn, Christine McCrary Sisk, Yale Mitchel, Richard C. Pasternak
American Heart Journal
February 2009 (Vol. 157, Issue 2, Pages 352-360.e2) Abstract |
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Bloomfield et al1 found no adverse effects of the cholesteryl ester transfer protein (CETP) inhibitor anacetrapib in an 8-week trial but did not measure its effect on vitamin E transport. High-density lipoprotein (HDL) is 3 to 5 times more effective than low-density lipoprotein at transporting vitamin E to endothelial cells,2 a process mediated by the scavenger receptor class B, type I (SR-BI).3 Vitamin E uptake is selective, occurring in 10-fold excess of HDL holoparticle uptake.4 In endothelial cells, vitamin E inhibits the expression of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin5; increases nitric oxide formation6; and inhibits the oxidative modification of extracellular low-density lipoprotein.7 A specific CETP inhibitor decreased the transfer of vitamin E from triglyceride-rich lipoproteins to HDL by 45% in vitro.8 An 8-week preliminary trial of the CETP inhibitor torcetrapib found no increase in adverse effects,9 but this drug ultimately increased the risk of cardiovascular events and death from all causes.10 Because part of the protective effect of HDL may be due to its role in vitamin E transport, safety and efficacy trials of CETP inhibitors should take into account their effect on this process.
References
1. 1Bloomfield D, Carlson GL, Sapre A, et al.Efficacy and safety of the cholesteryl ester transfer protein inhibitor anacetrapib as monotherapy and coadministered with atorvastatin in dyslipidemic patients. Am Heart J. 2009;157:352–360.e2. Abstract | Full Text |
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2. 2Goti D, Hammer A, Galla HJ, et al.Uptake of lipoprotein-associated alpha-tocopherol by primary porcine brain capillary endothelial cells. J Neurochem. 2000;74:1374–1383. MEDLINE |
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6. 6Heller R, Werner-Felmayer G, Werner ER. Alpha-tocopherol and endothelial nitric oxide synthesis. Ann NY Acad Sci. 2004;1031:74–85. MEDLINE |
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7. 7Steinbrecher UP, Parthasarathy S, Leake DS, et al.Modification of low density lipoprotein by endothelial cells involves lipid peroxidation and degradation of low density lipoprotein phospholipids. Proc Natl Acad Sci USA. 1984;81:3883–3887. MEDLINE |
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8. 8Hackquebard M, Vandenbranden M, Malaisse WJ, et al.Transfer from lipid emulsions to plasma lipoproteins: mediation by multiple mechanisms. Lipids.2008;43:663–671.
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9. 9McKenney JM, Davidson MH, Shear CL. Efficacy and safety of torcetrapib, a novel cholesteryl ester transfer protein inhibitor, in individuals with below-average high-density lipoprotein cholesterol levels on a background of atorvastatin. J Am Coll. Cardiol. 2006;48:1782–1790. Abstract | Full Text |
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10. 10Barter PJ, Caulfield M, Eriksson M. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007;357:2109–2122.
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