title: LDL-associated apolipoprotein J and lysozyme are associated with atherogenic properties of LDL found in type 2 diabetes and the metabolic syndrome.
abstract: OBJECTIVE
  Exchangeable low-density lipoprotein (LDL)-associated proteins can affect the atherogenic properties of LDL. Our aim was to analyse the protein composition of LDL from individuals with or without type 2 diabetes and the metabolic syndrome (T2DM) in relation to other LDL particle characteristics, to assess whether certain proteins associate more with certain subclasses of LDL typical for T2DM, such as small, apoCIII-rich LDL.
  
  
  METHODS
  Low-density lipoprotein from two cohorts of 61-year-old men (n = 19 and 64) with or without T2DM was isolated using size-exclusion chromatography or deuterium oxide-based ultracentrifugation. LDL-associated proteins were identified using mass spectrometry and quantified using two-dimensional gel electrophoresis or enzyme-linked immunosorbent assay. Differently expressed LDL-associated proteins apolipoprotein (apo)J and lysozyme were also measured in serum from a third cohort of women (n = 71) with or without T2DM. Lysozyme binding to advanced glycation end product (AGE)-LDL was examined in vitro.
  
  
  RESULTS
  ApoJ and lysozyme were increased in LDL particles with increased apoCIII content and decreased cholesterol content. When isolated with size-exclusion chromatography, LDL from individuals with T2DM contained more apoJ and lysozyme and less apoA1 than LDL from control individuals. LDL content of apoJ correlated with a smaller LDL particle size. Serum levels of lysozyme, but not apoJ, were increased in individuals with T2DM. In vitro, lysozyme associated more with AGE-LDL than with unmodified LDL.
  
  
  CONCLUSIONS
  Our results indicate that apoJ and lysozyme are increased in LDL with characteristics of small dense LDL in T2DM. Small dense LDL is easily glycated, and the increased affinity of lysozyme for AGE-LDL provides a possible partial explanation for an increase lysozyme in LDL from those with type 2 diabetes.
authors.affiliation: Department of Molecular and Clinical Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Pettersson
authors.forename: H
authors.initials: H
authors.lastname: Karlsson
authors.forename: M
authors.initials: M
authors.lastname: Ståhlman
authors.forename: T
authors.initials: T
authors.lastname: Larsson
authors.forename: B
authors.initials: B
authors.lastname: Fagerberg
authors.forename: M
authors.initials: M
authors.lastname: Lindahl
authors.forename: O
authors.initials: O
authors.lastname: Wiklund
authors.forename: J
authors.initials: J
authors.lastname: Borén
authors.forename: L
authors.initials: L
authors.lastname: Fogelstrand
mesh_terms: D002784:Cholesterol / Q000097:blood; D002850:Chromatography, Gel / Q000379:methods; D051152:Clusterin / Q000097:blood*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood*; D008875:Middle Aged; D009113:Muramidase / Q000097:blood*
chemical_list: C495242:CLU protein, human; D051152:Clusterin; D017127:Glycation End Products, Advanced; D008077:Lipoproteins, LDL; D002784:Cholesterol; D009113:Muramidase