title: Lipid oxidation in carriers of lecithin:cholesterol acyltransferase gene mutations.
abstract: OBJECTIVE
  Lecithin:cholesterol acyltransferase (LCAT) has been shown to play a role in the depletion of lipid oxidation products, but this has so far not been studied in humans. In this study, we investigated processes and parameters relevant to lipid oxidation in carriers of functional LCAT mutations.
  
  
  RESULTS
  In 4 carriers of 2 mutant LCAT alleles, 63 heterozygotes, and 63 family controls, we measured activities of LCAT, paraoxonase 1, and platelet-activating factor-acetylhydrolase; levels of lysophosphatidylcholine molecular species, arachidonic and linoleic acids, and their oxidized derivatives; immunodetectable oxidized phospholipids on apolipoprotein (apo) B-containing and apo(a)-containing lipoproteins; IgM and IgG autoantibodies to malondialdehyde-low-density lipoprotein and IgG and IgM apoB-immune complexes; and the antioxidant capacity of high-density lipoprotein (HDL). In individuals with LCAT mutations, plasma LCAT activity, HDL cholesterol, apoA-I, arachidonic acid, and its oxidized derivatives, oxidized phospholipids on apo(a)-containing lipoproteins, HDL-associated platelet-activating factor-acetylhydrolase activity, and the antioxidative capacity of HDL were gene-dose-dependently decreased. Oxidized phospholipids on apoB-containing lipoproteins was increased in heterozygotes (17%; P<0.001) but not in carriers of 2 defective LCAT alleles.
  
  
  CONCLUSIONS
  Carriers of LCAT mutations present with significant reductions in LCAT activity, HDL cholesterol, apoA-I, platelet-activating factor-acetylhydrolase activity, and antioxidative potential of HDL, but this is not associated with parameters of increased lipid peroxidation; we did not observe significant changes in the oxidation products of arachidonic acid and linoleic acid, immunoreactive oxidized phospholipids on apo(a)-containing lipoproteins, and IgM and IgG autoantibodies against malondialdehyde-low-density lipoprotein. These data indicate that plasma LCAT activity, HDL-associated platelet-activating factor-acetylhydrolase activity, and HDL cholesterol may not influence the levels of plasma lipid oxidation products.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Adriaan G
authors.initials: AG
authors.lastname: Holleboom
authors.forename: Georgios
authors.initials: G
authors.lastname: Daniil
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Fu
authors.forename: Renliang
authors.initials: R
authors.lastname: Zhang
authors.forename: G Kees
authors.initials: GK
authors.lastname: Hovingh
authors.forename: Alinda W
authors.initials: AW
authors.lastname: Schimmel
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: Erik S G
authors.initials: ES
authors.lastname: Stroes
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Witztum
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Hutten
authors.forename: Sotirios
authors.initials: S
authors.lastname: Tsimikas
authors.forename: Stanley L
authors.initials: SL
authors.lastname: Hazen
authors.forename: Angeliki
authors.initials: A
authors.lastname: Chroni
authors.forename: Jan Albert
authors.initials: JA
authors.lastname: Kuivenhoven
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism*; D000328:Adult; D000483:Alleles; D016632:Apolipoprotein A-I / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000378:metabolism*; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D015227:Lipid Peroxidation; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010084:Oxidation-Reduction; D010375:Pedigree; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000235:genetics* / Q000378:metabolism
chemical_list: D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D008055:Lipids; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase