American Heart Journal
Volume 158, Issue 1 , Page e11, July 2009

Effect of cholesteryl ester transfer protein inhibitor on vitamin E transport should be studied

Department of Nutritional Sciences, University of Connecticut, CT

Biochemical and Molecular Nutrition, University of Connecticut, CT

Article Outline

 

Bloomfield et al1 found no adverse effects of the cholesteryl ester transfer protein (CETP) inhibitor anacetrapib in an 8-week trial, but they 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.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.

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References 

  1. Bloomfield 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
  2. Goti 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
  3. Tachikawa M, Okayasu S, Hosoya K. Functional involvement of scavenger receptor class B, type I, in the uptake of alpha-tocopherol using cultured rat retinal capillary endothelial cells. Mol Vis. 2007;13:2041–2047
  4. Balazs Z, Panzenboeck U, Hammer A. Uptake and transport of high-density lipoprotein (HDL) and HDL-associated alpha-tocopherol by an in vitro blood-brain barrier model. J Neurochem. 2004;89:939–950
  5. van Dama B, van Hinsberghd VWM, Stehouwera CDA, et al. Vitamin E inhibits lipid peroxidation-induced adhesion molecule expression in endothelial cells and decreases soluble cell adhesion molecules in healthy subjects. Cardiovasc Res. 2003;57:563–571
  6. Heller R, Werner-Felmayer G, Werner ER. Alpha-tocopherol and endothelial nitric oxide synthesis. Ann N Y Acad Sci. 2004;1031:74–85
  7. Steinbrecher 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 U S A. 1984;81:3883–3887
  8. Hackquebard M, Vandenbranden M, Malaisse WJ. Vitamin E transfer from lipid emulsions to plasma lipoproteins: mediation by multiple mechanisms. Lipids. 2008;43:663–671
  9. McKenney 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
  10. Barter PJ, Caulfield M, Eriksson M. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007;357:2109–2122

PII: S0002-8703(09)00360-3

doi:10.1016/j.ahj.2009.05.004

American Heart Journal
Volume 158, Issue 1 , Page e11, July 2009

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