title: Characterization of antioxidant/anti-inflammatory properties and apoA-I-containing subpopulations of HDL from family subjects with monogenic low HDL disorders.
abstract: BACKGROUND
  Genetic factors regulate both high-density lipoprotein (HDL) levels and functionality, thus affecting HDL antiatherogenic properties. We characterized the HDL antioxidant/anti-inflammatory properties and apoA-I-containing subpopulations in families with monogenic low HDL disorders.
  
  
  METHODS
  Subjects with mutations in apolipoprotein A-I (apoA-I), ATP-binding cassette transporter A1 (ABCA1) or lecithin:cholesterol acyltransferase (LCAT) and family controls were studied. HDL antioxidant/anti-inflammatory properties were assayed by an in vitro fluorometric method and HDL-associated paraoxonase-1 (PON1), platelet activating factor-acetylhydrolase (PAF-AH), LCAT, malondialdehyde (MDA), PAF and serum amyloid A (SAA) were measured. ApoA-I-containing HDL subpopulations were analyzed by two-dimensional non-denaturing gel electrophoresis.
  
  
  RESULTS
  ApoA-I heterozygotes and subjects with partial or complete ABCA1 or LCAT deficiency had HDL with reduced antioxidant/anti-inflammatory properties and increased MDA levels. HDL-PON1 activity was reduced in apoA-I heterozygotes and in subjects with complete ABCA1 deficiency. HDL-PAF-AH activity was reduced in subjects with partial or complete ABCA1 deficiency or complete LCAT deficiency. HDL-LCAT activity was reduced in all LCAT mutation carriers. HDL-PAF levels were increased in apoA-I heterozygotes. HDL-SAA levels were increased in subjects with complete ABCA1 deficiency. ApoA-I, ABCA1 and LCAT heterozygotes were depleted of the large α1 HDL subpopulation. Subjects with complete LCAT deficiency showed mostly the small α4 HDL subpopulation and subjects with complete ABCA1 deficiency the α4 and preβ HDL subpopulations.
  
  
  CONCLUSIONS
  This study shows that mutations in apoA-I, ABCA1 and LCAT have direct effect on the antioxidant/anti-inflammatory properties of HDL. Furthermore, our study shows the effect of specific mutations on the apoA-I-containing HDL subpopulation profiles.
authors.affiliation: Institute of Biology, National Center for Scientific Research Demokritos, Agia Paraskevi, Athens 15310, Greece.
authors.forename: Georgios
authors.initials: G
authors.lastname: Daniil
authors.forename: Alexia A P
authors.initials: AA
authors.lastname: Phedonos
authors.forename: Adriaan G
authors.initials: AG
authors.lastname: Holleboom
authors.forename: Mohammad Mahdi
authors.initials: MM
authors.lastname: Motazacker
authors.forename: Letta
authors.initials: L
authors.lastname: Argyri
authors.forename: Jan Albert
authors.initials: JA
authors.lastname: Kuivenhoven
authors.forename: Angeliki
authors.initials: A
authors.lastname: Chroni
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D000975:Antioxidants / Q000378:metabolism*; D016632:Apolipoprotein A-I / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006579:Heterozygote; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008297:Male; D008659:Metabolic Diseases / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D010375:Pedigree; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000235:genetics
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D007862:Phosphatidylcholine-Sterol O-Acyltransferase