title: Increased cholesterol efflux capacity in metabolic syndrome: Relation with qualitative alterations in HDL and LCAT.
abstract: BACKGROUND
  Metabolic syndrome (MetS) is associated with changes in HDL levels, composition and sub-fraction profile. Whether these alterations affect HDL anti-atherogenic function, specifically measured as its capacity to perform cholesterol efflux, is not yet clearly known.
  
  
  OBJECTIVE
  To evaluate the relation between serum cholesterol efflux capacity and the changes in HDL composition and sub-fraction profile in MetS.
  
  
  METHODS
  In 35 non-treated MetS patients and 15 healthy controls, HDL mediated cholesterol efflux was measured as the ability of apoB-depleted serum to accept cholesterol from cholesterol-loaded BHK cells expressing either ABCA1 or ABCG1. Additionally we determined: lipid profile, HDL sub-fractions (NMR) and LCAT mass (ELISA). Isolated HDL (δ:1.063-1.210 g/mL) was chemically characterized. Pre-β1-HDL was determined by 2D-electrophoresis in a sub-group of MetS and controls (n = 6 each).
  
  
  RESULTS
  Surprisingly, MetS patients presented higher ABCA1 mediated cholesterol efflux (10.4 ± 1.8 vs. 8.7 ± 0.3%; p = 0.0001), without differences in ABCG1 efflux. In MetS, HDL showed reduction in particle size and number (p < 0.02) and lower large/small HDL ratio (p = 0.05), as well as triglyceride enrichment (p = 0.0001). Pre-β1-HDL was increased in MetS (p = 0.048) and correlated with ABCA1-cholesterol efflux (r = 0.64; p = 0.042). LCAT mass showed a tendency to reduction in MetS (p = 0.08), and inversely correlated with ABCA1-cholesterol efflux (r = -0.51; p = 0.001), independently of obesity and insulin-resistance (β = -0.40, p = 0.034).
  
  
  CONCLUSIONS
  This is the first description of ABCA1 mediated cholesterol efflux in MetS. Regardless the reduced HDL-cholesterol, in vitro cholesterol efflux capacity by ABCA1 was enhanced, linked to increased pre-β1-HDL and slightly reduced in LCAT mass that would probably reflect a delay in reverse cholesterol transport occurring in MetS.
authors.affiliation: Laboratory of Lipids and Atherosclerosis, Department of Clinical Biochemistry, Faculty of Pharmacy and Biochemistry, INFIBIOC, University of Buenos Aires, Argentina; Lipoprotein Metabolism Section, National Heart, Lung, Blood Institute, National Institutes of Health, Bethesda, Maryland, USA. Electronic address: dmlucero@ffyb.uba.ar.
authors.forename: Diego
authors.initials: D
authors.lastname: Lucero
authors.forename: Denis
authors.initials: D
authors.lastname: Sviridov
authors.affiliation: Lipoprotein Metabolism Section, National Heart, Lung, Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Denis
authors.initials: D
authors.lastname: Svidirov
authors.affiliation: Lipoprotein Metabolism Section, National Heart, Lung, Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Lita
authors.initials: L
authors.lastname: Freeman
authors.affiliation: Laboratory of Lipids and Atherosclerosis, Department of Clinical Biochemistry, Faculty of Pharmacy and Biochemistry, INFIBIOC, University of Buenos Aires, Argentina.
authors.forename: Graciela I
authors.initials: GI
authors.lastname: López
authors.affiliation: Department of Gastroenterology, National Hospital "Prof. A. Posadas", Buenos Aires, Argentina.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Fassio
authors.affiliation: Lipoprotein Metabolism Section, National Heart, Lung, Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Alan T
authors.initials: AT
authors.lastname: Remaley
authors.affiliation: Laboratory of Lipids and Atherosclerosis, Department of Clinical Biochemistry, Faculty of Pharmacy and Biochemistry, INFIBIOC, University of Buenos Aires, Argentina.
authors.forename: Laura
authors.initials: L
authors.lastname: Schreier
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002460:Cell Line; D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood*; D006224:Cricetinae; D005260:Female; D053442:High-Density Lipoproteins, Pre-beta / Q000097:blood; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics; D008875:Middle Aged; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism*; D014162:Transfection
chemical_list: C577836:ABCA1 protein, human; C419353:ABCG1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D015415:Biomarkers; D008076:Cholesterol, HDL; D053442:High-Density Lipoproteins, Pre-beta; D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase
keywords: Cholesterol efflux capacity; HDL; LCAT; Metabolic syndrome; Pre-β1-HDL