title: Inhibition of cholesteryl ester transfer protein by torcetrapib modestly increases macrophage cholesterol efflux to HDL.
abstract: OBJECTIVE
  This study examines the effects of pharmacological inhibition of cholesteryl ester transfer protein (CETP) on the ability of high-density lipoprotein particles (HDL) to promote net cholesterol efflux from human THP-1 macrophage foam cells.
  
  
  RESULTS
  Two groups of 8 healthy, moderately hyperlipidemic subjects received the CETP inhibitor torcetrapib at 60 or 120 mg daily for 8 weeks. Torcetrapib increased HDL cholesterol levels in both groups by 50% and 60%, respectively. Compared with baseline, torcetrapib 60 mg daily increased HDL-mediated net cholesterol efflux from foam cells primarily by increasing HDL concentrations, whereas 120 mg daily torcetrapib increased cholesterol efflux both by increasing HDL concentration and by causing increased efflux at matched HDL concentrations. There was an increased content of lecithin:cholesterol acyltransferase (LCAT) and apolipoprotein E (apoE) in HDL-2 only at the 120 mg dose. ABCG1 activity was responsible for 40% to 50% of net cholesterol efflux to both control and T-HDL.
  
  
  CONCLUSIONS
  These data indicate that inhibition of CETP by torcetrapib causes a modest increase in the ability of HDL to promote net cholesterol efflux at the 60 mg dose, and a more dramatic increase at the 120 mg dose in association with enhanced particle functionality.
authors.affiliation: Division of Molecular Medicine, Department of Medicine, Columbia University, 630 West 168 St, New York, NY 10032, USA. ly2159@columbia.edu
authors.forename: Laurent
authors.initials: L
authors.lastname: Yvan-Charvet
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Matsuura
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Bamberger
authors.forename: Tu
authors.initials: T
authors.lastname: Nguyen
authors.forename: Franz
authors.initials: F
authors.lastname: Rinninger
authors.forename: Xian-Cheng
authors.initials: XC
authors.lastname: Jiang
authors.forename: Charles L
authors.initials: CL
authors.lastname: Shear
authors.forename: Alan R
authors.initials: AR
authors.lastname: Tall
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001057:Apolipoproteins E / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology; D015153:Blotting, Western; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008076:Cholesterol, HDL / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011804:Quinolines / Q000008:administration & dosage* / Q000627:therapeutic use; D002785:Sterol O-Acyltransferase / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D001057:Apolipoproteins E; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D011804:Quinolines; C483909:torcetrapib; D002785:Sterol O-Acyltransferase