title: Advanced glycated albumin impairs HDL anti-inflammatory activity and primes macrophages for inflammatory response that reduces reverse cholesterol transport.
abstract: OBJECTIVE
  We investigated the effect of advanced glycated albumin (AGE-albumin) on macrophage sensitivity to inflammation elicited by S100B calgranulin and lipopolysaccharide (LPS) and the mechanism by which HDL modulates this response. We also measured the influence of the culture medium, isolated from macrophages treated with AGE-albumin, on reverse cholesterol transport (RCT).
  
  
  RESULTS
  Macrophages were incubated with control (C) or AGE-albumin in the presence or absence of HDL, followed by incubations with S100B or LPS. Also, culture medium obtained from cells treated with C- or AGE-albumin, following S100B or LPS stimulation was utilized to treat naive macrophages in order to evaluate cholesterol efflux and the expression of HDL receptors. In comparison with C-albumin, AGE-albumin, promoted a greater secretion of cytokines after stimulation with S100B or LPS. A greater amount of cytokines was also produced by macrophages treated with AGE-albumin even in the presence of HDL. Cytokine-enriched medium, drawn from incubations with AGE-albumin and S100B or LPS impaired the cholesterol efflux mediated by apoA-I (23% and 37%, respectively), HDL(2) (43% and 47%, respectively) and HDL(3) (20% and 8.5%, respectively) and reduced ABCA-1 protein level (16% and 26%, respectively).
  
  
  CONCLUSIONS
  AGE-albumin primes macrophages for an inflammatory response impairing the RCT. Moreover, AGE-albumin abrogates the anti-inflammatory role of HDL, which may aggravate the development of atherosclerosis in DM.
authors.affiliation: Lipids Laboratory (LIM 10), University of São Paulo Medical School, São Paulo, SP, Brazil.
authors.forename: Ligia S
authors.initials: LS
authors.lastname: Okuda
authors.forename: Gabriela
authors.initials: G
authors.lastname: Castilho
authors.forename: Debora D F M
authors.initials: DD
authors.lastname: Rocco
authors.forename: Edna R
authors.initials: ER
authors.lastname: Nakandakare
authors.forename: Sergio
authors.initials: S
authors.lastname: Catanozi
authors.forename: Marisa
authors.initials: M
authors.lastname: Passarelli
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000737:chemistry / Q000494:pharmacology*; D015151:Immunoblotting; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000494:pharmacology; D051122:Scavenger Receptors, Class B / Q000378:metabolism; D012709:Serum Albumin / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C419353:ABCG1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D016207:Cytokines; D017127:Glycation End Products, Advanced; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D008075:Lipoproteins, HDL; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; C579159:S100b protein, mouse; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D012709:Serum Albumin; D002784:Cholesterol