title: The inflammatory properties of electronegative low-density lipoprotein from type 1 diabetic patients are related to increased platelet-activating factor acetylhydrolase activity.
abstract: OBJECTIVE
  Chemical and biological characteristics of LDL(-) from type 1 diabetic subjects were analysed. The diabetic patients were studied during poor and optimised glycaemic control.
  
  
  METHODS
  Total LDL was subfractionated into electropositive LDL(+) and electronegative LDL(-) by anion exchange chromatography and the lipid and protein composition of the two determined.
  
  
  RESULTS
  LDL(-) differed from LDL(+) in that it had higher triglyceride, non-esterified fatty acids, apoE, apoC-III and platelet-activating factor acetylhydrolase (PAF-AH), as well as lower apoB relative content. No evidence of increased oxidation was observed in LDL(-). LDL(-) increased two-fold the release of interleukin 8 (IL-8) and monocyte chemotactic protein 1 (MCP-1) in endothelial cells, suggesting an inflammatory role. Optimisation of glycaemic control after insulin therapy decreased the proportion of LDL(-), but did not modify the composition of LDL subfractions, except for a decrease in PAF-AH activity in LDL(-). The possibility that LDL(-) could be generated by non-enzymatic glycosylation was studied. Fructosamine and glycated LDL content in LDL subfractions from type 1 diabetic patients was greater than in LDL subfractions isolated from normoglycaemic subjects, and decreased after glycaemic optimisation in both subfractions. However, no difference was observed between LDL(+) and LDL(-) before and after insulin therapy.
  
  
  CONCLUSIONS
  These results provide evidence that LDL(-) is not produced by glycosylation. Nevertheless, LDL(-) from diabetic patients displays inflammatory potential reflected by the induction of chemokine release in endothelial cells. This proatherogenic effect could be related to the high PAF-AH activity in LDL(-).
authors.affiliation: Department of Biochemistry, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Sánchez-Quesada
authors.forename: S
authors.initials: S
authors.lastname: Benítez
authors.forename: A
authors.initials: A
authors.lastname: Pérez
authors.forename: A M
authors.initials: AM
authors.lastname: Wagner
authors.forename: M
authors.initials: M
authors.lastname: Rigla
authors.forename: G
authors.initials: G
authors.lastname: Carreras
authors.forename: L
authors.initials: L
authors.lastname: Vila
authors.forename: M
authors.initials: M
authors.lastname: Camacho
authors.forename: R
authors.initials: R
authors.lastname: Arcelus
authors.forename: J
authors.initials: J
authors.lastname: Ordóñez-Llanos
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism*; D001059:Apoproteins / Q000737:chemistry; D001786:Blood Glucose / Q000378:metabolism; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D018925:Chemokines / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000473:pathology; D004591:Electrophoresis, Polyacrylamide Gel; D042783:Endothelial Cells / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000737:chemistry* / Q000633:toxicity*; D008315:Malondialdehyde / Q000378:metabolism; D010084:Oxidation-Reduction; D014157:Transcription Factors
chemical_list: D001059:Apoproteins; D001786:Blood Glucose; D018925:Chemokines; D008055:Lipids; D008077:Lipoproteins, LDL; D014157:Transcription Factors; D008315:Malondialdehyde; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase