title: Functionality of postprandial larger HDL2 particles is enhanced following CETP inhibition therapy.
abstract: OBJECTIVE
  To evaluate the impact of CETP inhibition on the capacity of individual postprandial HDL subspecies to promote key steps of the reverse cholesterol transport pathway.
  
  
  METHODS
  The capacity of HDL particles to mediate cellular free cholesterol efflux and selective hepatic uptake of cholesteryl esters was evaluated throughout postprandial phase (0-8 h) following consumption of a standardised mixed meal before and after treatment for 6 weeks with atorvastatin alone (10 mg/d) and subsequently with combination torcetrapib/atorvastatin (60/10 mg/d) in 16 patients displaying low HDL-C levels (<40 mg/dl).
  
  
  RESULTS
  The larger HDL2b and HDL2a subfraction displayed a superior capacity to mediate cellular free cholesterol efflux via both SR-BI and ABCG1-dependent pathways than smaller HDL3 subspecies. CETP inhibition specifically enhanced the capacity of HDL2b subfraction for both SR-BI and ABCG1 dependent efflux. However, only the SR-BI-dependent efflux to HDL2b subspecies can be further enhanced during postprandial lipemia following CETP inhibition. Concomitantly, postprandial lipemia was associated with a reduced capacity of total HDL particles to deliver cholesteryl esters to hepatic cells in a drug independent manner.
  
  
  CONCLUSIONS
  CETP inhibition specifically improves postprandial SR-BI and ABCG1-dependent efflux to larger HDL2b subspecies. In addition, CETP inhibition improves HDL-CE delivery to hepatic cells and maintains an efficient direct return of cholesteryl esters to the liver during postprandial lipemia.
authors.affiliation: INSERM UMRS939, Hôpital de la Pitié, Paris, France.
authors.forename: Natacha
authors.initials: N
authors.lastname: Bellanger
authors.forename: Zélie
authors.initials: Z
authors.lastname: Julia
authors.forename: Elise F
authors.initials: EF
authors.lastname: Villard
authors.forename: Petra
authors.initials: P
authors.lastname: El Khoury
authors.forename: Emilie
authors.initials: E
authors.lastname: Duchene
authors.forename: M John
authors.initials: MJ
authors.lastname: Chapman
authors.forename: Natalie
authors.initials: N
authors.lastname: Fournier
authors.forename: Wilfried
authors.initials: W
authors.lastname: Le Goff
authors.forename: Maryse
authors.initials: M
authors.lastname: Guerin
mesh_terms: D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood; D016633:Apolipoprotein A-II / Q000097:blood; D000069059:Atorvastatin; D018955:CD36 Antigens / Q000378:metabolism; D016466:CHO Cells; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002788:Cholesterol Esters / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D006224:Cricetinae; D003412:Cricetulus; D004359:Drug Therapy, Combination; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D053439:Lipoproteins, HDL2 / Q000097:blood*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D010297:Paris; D010316:Particle Size; D019518:Postprandial Period; D011758:Pyrroles / Q000627:therapeutic use*; D011804:Quinolines / Q000627:therapeutic use*; D013997:Time Factors; D014162:Transfection; D016896:Treatment Outcome
chemical_list: C419353:ABCG1 protein, human; C505693:APOA1 protein, human; C115794:APOA2 protein, human; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D018955:CD36 Antigens; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D008076:Cholesterol, HDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D053439:Lipoproteins, HDL2; D011758:Pyrroles; D011804:Quinolines; C483909:torcetrapib; D000069059:Atorvastatin