title: Effect of inhibiting cholesteryl ester transfer protein on the kinetics of high-density lipoprotein cholesteryl ester transport in plasma: in vivo studies in rabbits.
abstract: OBJECTIVE
  Inhibitors of cholesteryl ester transfer protein (CETP) have been developed as potential anti-atherogenic agents. Theoretically, however, they may be pro-atherogenic by blocking one of the pathways for removing high-density lipoprotein (HDL) cholesteryl esters (CE) from plasma in the final step of reverse cholesterol transport. Here we describe how CETP inhibition in rabbits impacts on the kinetics of HDL CE transport in plasma.
  
  
  RESULTS
  Administration of a CETP inhibitor reduced CETP activity by 80% to 90% and doubled the HDL cholesteryl ester concentration. Multi-compartmental analysis was used to determine HDL CE kinetics in CETP-inhibited and control rabbits after injection of tracer amounts of both native and reconstituted HDL labeled with 3H in the CE moiety. In control rabbits, HDL CE was removed from plasma by both a direct pathway and an indirect pathway after transfer of HDL CE to the very-low-density lipoprotein/low-density lipoprotein fraction. In CETP-inhibited rabbits there was an almost complete block in removal via the indirect pathway. This did not compromise the overall removal of HDL CE from plasma, which was not different in control and inhibited animals.
  
  
  CONCLUSIONS
  Inhibiting CETP in rabbits does not compromise the removal of HDL CE from plasma.
authors.affiliation: Royal Adelaide Hospital, Adelaide, Australia.
authors.forename: P
authors.initials: P
authors.lastname: Kee
authors.forename: D
authors.initials: D
authors.lastname: Caiazza
authors.forename: K-A
authors.initials: KA
authors.lastname: Rye
authors.forename: P H R
authors.initials: PH
authors.lastname: Barrett
authors.forename: L A
authors.initials: LA
authors.lastname: Morehouse
authors.forename: P J
authors.initials: PJ
authors.lastname: Barter
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D002784:Cholesterol / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000097:blood* / Q000378:metabolism; D006023:Glycoproteins / Q000037:antagonists & inhibitors*; D007700:Kinetics; D050356:Lipid Metabolism; D008075:Lipoproteins, HDL / Q000097:blood*; D008954:Models, Biological; D011804:Quinolines / Q000008:administration & dosage*; D011817:Rabbits; D014316:Tritium
chemical_list: C511686:CP-456,643; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D006023:Glycoproteins; C059714:HDL cholesteryl ester; D008075:Lipoproteins, HDL; D011804:Quinolines; D014316:Tritium; D002784:Cholesterol