title: ApoCIII-enriched LDL in type 2 diabetes displays altered lipid composition, increased susceptibility for sphingomyelinase, and increased binding to biglycan.
abstract: OBJECTIVE
  Apolipoprotein CIII (apoCIII) is an independent risk factor for cardiovascular disease, but the molecular mechanisms involved are poorly understood. We investigated potential proatherogenic properties of apoCIII-containing LDL from hypertriglyceridemic patients with type 2 diabetes.
  
  
  METHODS
  LDL was isolated from control subjects, subjects with type 2 diabetes, and apoB transgenic mice. LDL-biglycan binding was analyzed with a solid-phase assay using immunoplates coated with biglycan. Lipid composition was analyzed with mass spectrometry. Hydrolysis of LDL by sphingomyelinase was analyzed after labeling plasma LDL with [(3)H]sphingomyelin. ApoCIII isoforms were quantified after isoelectric focusing. Human aortic endothelial cells were incubated with desialylated apoCIII or with LDL enriched with specific apoCIII isoforms.
  
  
  RESULTS
  We showed that enriching LDL with apoCIII only induced a small increase in LDL-proteoglycan binding, and this effect was dependent on a functional site A in apoB100. Our findings indicated that intrinsic characteristics of the diabetic LDL other than apoCIII are responsible for further increased proteoglycan binding of diabetic LDL with high-endogenous apoCIII, and we showed alterations in the lipid composition of diabetic LDL with high apoCIII. We also demonstrated that high apoCIII increased susceptibility of LDL to hydrolysis and aggregation by sphingomyelinases. In addition, we demonstrated that sialylation of apoCIII increased with increasing apoCIII content and that sialylation of apoCIII was essential for its proinflammatory properties.
  
  
  CONCLUSIONS
  We have demonstrated a number of features of apoCIII-containing LDL from hypertriglyceridemic patients with type 2 diabetes that could explain the proatherogenic role of apoCIII.
authors.affiliation: Department of Medicine, Helsinki University Central Hospital and Biomedicum, Helsinki, Finland.
authors.forename: Anne
authors.initials: A
authors.lastname: Hiukka
authors.forename: Marcus
authors.initials: M
authors.lastname: Ståhlman
authors.forename: Camilla
authors.initials: C
authors.lastname: Pettersson
authors.forename: Malin
authors.initials: M
authors.lastname: Levin
authors.forename: Martin
authors.initials: M
authors.lastname: Adiels
authors.forename: Susanne
authors.initials: S
authors.lastname: Teneberg
authors.forename: Eeva S
authors.initials: ES
authors.lastname: Leinonen
authors.forename: Lillemor Mattsson
authors.initials: LM
authors.lastname: Hultén
authors.forename: Olov
authors.initials: O
authors.lastname: Wiklund
authors.forename: Matej
authors.initials: M
authors.lastname: Oresic
authors.forename: Sven-Olof
authors.initials: SO
authors.lastname: Olofsson
authors.forename: Marja-Riitta
authors.initials: MR
authors.lastname: Taskinen
authors.forename: Kim
authors.initials: K
authors.lastname: Ekroos
authors.forename: Jan
authors.initials: J
authors.lastname: Borén
mesh_terms: D000368:Aged; D000818:Animals; D053305:Apolipoprotein C-III / Q000097:blood* / Q000378:metabolism; D001055:Apolipoproteins B / Q000235:genetics / Q000378:metabolism; D058578:Biglycan; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D006868:Hydrolysis; D015228:Hypertriglyceridemia / Q000453:epidemiology / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D011509:Proteoglycans / Q000378:metabolism*; D012307:Risk Factors; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism*
chemical_list: D053305:Apolipoprotein C-III; D001055:Apolipoproteins B; C546884:BGN protein, human; C546885:Bgn protein, mouse; D058578:Biglycan; D016326:Extracellular Matrix Proteins; D008077:Lipoproteins, LDL; D011509:Proteoglycans; D013108:Sphingomyelin Phosphodiesterase