title: Inhibition of CETP by torcetrapib attenuates the atherogenicity of postprandial TG-rich lipoproteins in type IIB hyperlipidemia.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the impact of torcetrapib on atherogenic TG-rich lipoprotein subfractions in the postprandial phase in Type IIB hyperlipidemia.
  
  
  RESULTS
  The quantitative and qualitative features of the postprandial profile of TG-rich lipoproteins were determined at baseline, after treatment for 6 weeks with 10 mg/d atorvastatin, and subsequently with an atorvastatin/torcetrapib combination (10/60 mg/d) in Type IIB patients (n=18). After ingestion of a standardized mixed meal, TG-rich lipoprotein subfractions were evaluated over 8 hours after each experimental period. On a background of atorvastatin, torcetrapib significantly attenuated the incremental postprandial area under the curve (iAUC 0 to 8 hours) for VLDL-1 (-40%), and the AUC 0 to 8 hours for VLDL-2 (-53%), with minor effect on chylomicron iAUC (-24%); concomitantly, the CE/TG ratio in both VLDL-1 and VLDL-2 was significantly reduced (-27% to -42%). Such reduction was attributable to torcetrapib-mediated attenuation of postprandial CE transfer to Chylomicrons (-17%) and VLDL-1 (-33%). Marked reduction in postprandial VLDL-1 levels was associated with apoE enrichment.
  
  
  CONCLUSIONS
  On a background of atorvastatin, torcetrapib attenuated the quantitative and qualitative features of the atherogenic postprandial profile of chylomicrons, VLDL-1 and VLDL-2. Such changes reflect the sum of torcetrapib-mediated effects on TG-rich lipoprotein production, intravascular remodeling, and catabolism.
authors.affiliation: INSERM Unité 551, Hôpital de la Pitié, Pavillon Benjamin Delessert, 83, 75651 Paris Cedex 13, France. mguerin@chups.jussieu.fr
authors.forename: Maryse
authors.initials: M
authors.lastname: Guerin
authors.forename: Wilfried
authors.initials: W
authors.lastname: Le Goff
authors.forename: Emilie
authors.initials: E
authors.lastname: Duchene
authors.forename: Zélie
authors.initials: Z
authors.lastname: Julia
authors.forename: Tu
authors.initials: T
authors.lastname: Nguyen
authors.forename: Tom
authors.initials: T
authors.lastname: Thuren
authors.forename: Charles L
authors.initials: CL
authors.lastname: Shear
authors.forename: M John
authors.initials: MJ
authors.lastname: Chapman
mesh_terms: D000328:Adult; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D000069059:Atorvastatin; D053480:Cholesterol Ester Transfer Proteins / Q000187:drug effects; D002914:Chylomicrons / Q000187:drug effects; D004041:Dietary Fats / Q000378:metabolism; D004044:Dietary Proteins / Q000378:metabolism; D004359:Drug Therapy, Combination; D006538:Heptanoic Acids / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy*; D008079:Lipoproteins, VLDL / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period / Q000187:drug effects*; D011758:Pyrroles / Q000627:therapeutic use; D011804:Quinolines / Q000494:pharmacology*
chemical_list: D000924:Anticholesteremic Agents; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D002914:Chylomicrons; D004041:Dietary Fats; D004044:Dietary Proteins; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008079:Lipoproteins, VLDL; D011758:Pyrroles; D011804:Quinolines; C483909:torcetrapib; D000069059:Atorvastatin