title: Inflammation modulates human HDL composition and function in vivo.
abstract: OBJECTIVE
  Inflammation may directly impair HDL functions, in particular reverse cholesterol transport (RCT), but limited data support this concept in humans.
  
  
  RESULTS
  We employed low-dose human endotoxemia to assess the effects of inflammation on HDL and RCT-related parameters in vivo. Endotoxemia induced remodelling of HDL with depletion of pre-β1a HDL particles determined by 2-D gel electrophoresis (-32.2±9.3% at 24 h, p<0.05) as well as small (-23.0±5.1%, p<0.01, at 24 h) and medium (-57.6±8.0% at 16 h, p<0.001) HDL estimated by nuclear magnetic resonance (NMR). This was associated with induction of class II secretory phospholipase A2 (~36 fold increase) and suppression of lecithin:cholesterol acyltransferase activity (-20.8±3.4% at 24 h, p<0.01) and cholesterol ester transfer protein mass (-22.2±6.8% at 24 h, p<0.001). The HDL fraction, isolated following endotoxemia, had reduced capacity to efflux cholesterol in vitro from SR-BI and ABCA1, but not ABCG1 transporter cell models.
  
  
  CONCLUSIONS
  These data support the concept that "atherogenic-HDL dysfunction" and impaired RCT occur in human inflammatory syndromes, largely independent of changes in plasma HDL-C and ApoA-I levels.
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Margarita
authors.initials: M
authors.lastname: de la Llera Moya
authors.forename: Fiona C
authors.initials: FC
authors.lastname: McGillicuddy
authors.forename: Christine C
authors.initials: CC
authors.lastname: Hinkle
authors.forename: Michael
authors.initials: M
authors.lastname: Byrne
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Joshi
authors.forename: Vihn
authors.initials: V
authors.lastname: Nguyen
authors.forename: Jennifer
authors.initials: J
authors.lastname: Tabita-Martinez
authors.forename: Megan L
authors.initials: ML
authors.lastname: Wolfe
authors.forename: Karen
authors.initials: K
authors.lastname: Badellino
authors.forename: Leticia
authors.initials: L
authors.lastname: Pruscino
authors.forename: Nehal N
authors.initials: NN
authors.lastname: Mehta
authors.forename: Bela F
authors.initials: BF
authors.lastname: Asztalos
authors.forename: Muredach P
authors.initials: MP
authors.lastname: Reilly
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000328:Adult; D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood; D002460:Cell Line; D053480:Cholesterol Ester Transfer Proteins / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood*; D015180:Electrophoresis, Gel, Two-Dimensional; D019446:Endotoxemia / Q000097:blood / Q000150:complications; D005260:Female; D054501:Group II Phospholipases A2 / Q000378:metabolism; D053442:High-Density Lipoproteins, Pre-beta / Q000097:blood*; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000209:etiology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D010316:Particle Size; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism; D051381:Rats; D051122:Scavenger Receptors, Class B / Q000378:metabolism; D013997:Time Factors; D055815:Young Adult
chemical_list: C577836:ABCA1 protein, human; C419353:ABCG1 protein, human; C505693:APOA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D053442:High-Density Lipoproteins, Pre-beta; D051122:Scavenger Receptors, Class B; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D054501:Group II Phospholipases A2