title: Advanced glycated albumin isolated from poorly controlled type 1 diabetes mellitus patients alters macrophage gene expression impairing ABCA-1-mediated reverse cholesterol transport.
abstract: BACKGROUND
  We evaluated the effects of albumin isolated from control individuals and from patients with poorly controlled type 1 diabetes mellitus on macrophage gene expression and on reverse cholesterol transport.
  
  
  METHODS
  Serum albumin was purified from control subjects (n = 12) and from patients with poorly controlled type 1 diabetes mellitus (n = 13). (14)C-cholesterol-labelled J774 macrophages treated with albumin were employed to measure cholesterol efflux mediated by apo A-I, HDL(3) or HDL(2), the intracellular lipid accumulation and the cellular ABCA-1 protein content. Agilent arrays (44000 probes) were used to analyse gene expression. Several differentially expressed genes were validated by real-time reverse transcription-PCR using TaqMan Two Step RT-PCR.
  
  
  RESULTS
  Levels of glycation-modified and (carboxymethyl)lysine-modified albumin were higher in diabetic patients than in control subjects. Apo A-I-mediated and HDL(2)-mediated cellular cholesterol efflux were impaired in macrophages treated with albumin from diabetic patients in comparison with control albumin-treated cells, which was attributed to the reduction in ABCA-1 protein content. Even in the presence of cholesterol acceptors, a higher level of intracellular lipid was observed in macrophages exposed to albumin from diabetic individuals in comparison with the control. The reduction in ABCA-1 content was associated with enhanced expression of stearoyl CoA desaturase 1 and decreased expression of janus kinase 2, which were induced by albumin from patients with type 1 diabetes mellitus.
  
  
  CONCLUSIONS
  (Carboxymethyl)lysine-modified albumin isolated from poorly controlled type 1 diabetic patients impairs ABCA-1-mediated reverse cholesterol transport and elicits intracellular lipid accumulation, possibly contributing to atherosclerosis.
authors.affiliation: Lipids Laboratory (LIM 10), Faculty of Medical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Adriana
authors.initials: A
authors.lastname: Machado-Lima
authors.forename: Rodrigo T
authors.initials: RT
authors.lastname: Iborra
authors.forename: Raphael S
authors.initials: RS
authors.lastname: Pinto
authors.forename: Camila H
authors.initials: CH
authors.lastname: Sartori
authors.forename: Erika R
authors.initials: ER
authors.lastname: Oliveira
authors.forename: Edna R
authors.initials: ER
authors.lastname: Nakandakare
authors.forename: José T
authors.initials: JT
authors.lastname: Stefano
authors.forename: Daniel
authors.initials: D
authors.lastname: Giannella-Neto
authors.forename: Maria Lucia C
authors.initials: ML
authors.lastname: Corrêa-Giannella
authors.forename: Marisa
authors.initials: M
authors.lastname: Passarelli
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D001692:Biological Transport / Q000502:physiology; D002784:Cholesterol / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D017127:Glycation End Products, Advanced / Q000235:genetics / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008075:Lipoproteins, HDL / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D012709:Serum Albumin / Q000235:genetics / Q000378:metabolism*
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D017127:Glycation End Products, Advanced; D008075:Lipoproteins, HDL; D012709:Serum Albumin; D002784:Cholesterol