title: Cholesteryl-ester transfer protein enhances the ability of high-density lipoprotein to inhibit low-density lipoprotein oxidation.
abstract: Therapeutic strategies to increase high-density lipoprotein (HDL) to treat or prevent vascular disease include the use of cholesteryl-ester transfer protein (CETP) inhibitors. Here, we show, to the best of our knowledge for the first time, that addition of CETP to HDL enhances the ability of HDL to inhibit low-density lipoprotein oxidation by ∼ 30% for total HDL and HDL(2) (both P < 0.05) and 75% for HDL(3) (P < 0.01). Therefore, CETP inhibition may be detrimental to the antiatherosclerotic properties of HDL, and these findings may partly explain the failure of the CETP inhibitor, torcetrapib, treatment to retard vascular disease despite large increases in HDL, in addition to its "off target" toxicity, a property which appears not to be shared by other members of this class of CETP inhibitor currently under clinical trial. Further, detailed studies are urgently required.
authors.affiliation: Division of Cardiovascular Sciences, University of Manchester, Manchester, UK.
authors.forename: David
authors.initials: D
authors.lastname: Hine
authors.forename: Bharti
authors.initials: B
authors.lastname: Mackness
authors.forename: Mike
authors.initials: M
authors.lastname: Mackness
mesh_terms: D053480:Cholesterol Ester Transfer Proteins / Q000378:metabolism*; D006801:Humans; D055256:Infectious Disease Incubation Period; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010084:Oxidation-Reduction
chemical_list: D053480:Cholesterol Ester Transfer Proteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL