title: Glycated albumin induces lipid infiltration in mice aorta independently of DM and RAS local modulation by inducing lipid peroxidation and inflammation.
abstract: Advanced glycated albumin (AGE-albumin) adversely impairs macrophage lipid homeostasis in vitro, which may be prevented by angiotensin receptor blockers. In vivo studies are inconclusive whether AGE-albumin itself plays important role in early-stage atherogenesis. We aimed at investigating how AGE-albumin by itself drives atherosclerosis development in dyslipidemic non-diabetic mice and if its effects are due to the activation of renin-angiotensin system in the arterial wall and the expression of genes and proteins involved in lipid flux.
  
  
  
  Murine albumin glycation was induced by incubation with 10mM glycolaldehyde and C-albumin with PBS alone. Twelve-week-old-male apoE knockout mice were submitted to a daily IP injection of control (C) or AGE-albumin (2mg/mL) during 30days with or without losartan (LOS: 100mg/L; C+LOS and AGE+LOS). Aortic arch was removed, and gene expression was determined by RT-PCR and protein content by immunofluorescence. Plasma lipid and glucose levels were similar among groups. Systolic blood pressure was similarly reduced in both groups treated with LOS. In comparison to C-albumin, aortic lipid infiltration was 5.3 times increased by AGE-albumin, which was avoided by LOS. LOS prevented the enhancement induced by AGE-albumin in Ager, Tnf and Cybb mRNA levels but did not reduce Olr1. Nfkb and Agt mRNA levels were unchanged by AGE-albumin. LOS similarly reduced Agtr1a mRNA level in both C and AGE-albumin groups. In AGE-albumin-treated mice, immunofluorescence for carboxymethyl-lysine, 4-hydroxynonenal and RAGE was respectively, 4.8, 2.6 and 1.7 times enhanced in comparison to C-albumin. These increases were all avoided by LOS.
  
  
  
  AGE-albumin evokes a pre-stage of atherogenesis in dyslipidemic mice independently of the presence of diabetes mellitus or modulation in the RAS in part by the induction of lipid peroxidation and inflammation.
authors.affiliation: Lipids Laboratory (LIM 10), Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Diego Juvenal
authors.initials: DJ
authors.lastname: Gomes
authors.affiliation: Rheumatology Division (LIM 17), Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Velosa
authors.affiliation: Lipids Laboratory (LIM 10), Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Ligia Shimabukuro
authors.initials: LS
authors.lastname: Okuda
authors.affiliation: Lipids Laboratory (LIM 10), Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Fernanda Bueno
authors.initials: FB
authors.lastname: Fusco
authors.affiliation: Lipids Laboratory (LIM 10), Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Karolinne Santana
authors.initials: KS
authors.lastname: da Silva
authors.affiliation: Lipids Laboratory (LIM 10), Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Paula Ramos
authors.initials: PR
authors.lastname: Pinto
authors.affiliation: Lipids Laboratory (LIM 10), Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Edna Regina
authors.initials: ER
authors.lastname: Nakandakare
authors.affiliation: Laboratory of Carbohydrates and Radioimuneassays (LIM 18), Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Maria Lucia
authors.initials: ML
authors.lastname: Correa-Giannella
authors.affiliation: School of Chemical Sciences and School of Biological Sciences, The University of Auckland, Auckland, New Zealand.
authors.forename: Tom
authors.initials: T
authors.lastname: Woods
authors.affiliation: School of Chemical Sciences and School of Biological Sciences, The University of Auckland, Auckland, New Zealand.
authors.forename: Margaret Anne
authors.initials: MA
authors.lastname: Brimble
authors.affiliation: Bioanalytical Mass Spectrometry Facility, The University of New South Wales, Sydney, Australia.
authors.forename: Russell
authors.initials: R
authors.lastname: Pickford
authors.affiliation: Lipid Research Group, School of Medical Sciences, Faculty of Medicine, The University of New South Wales, Sydney, Australia.
authors.forename: Kerry-Anne
authors.initials: KA
authors.lastname: Rye
authors.affiliation: Rheumatology Division (LIM 17), Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Walcy Rosolia
authors.initials: WR
authors.lastname: Teodoro
authors.affiliation: Lipids Laboratory (LIM 10), Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Sergio
authors.initials: S
authors.lastname: Catanozi
authors.affiliation: Lipids Laboratory (LIM 10), Medical School, University of São Paulo, São Paulo, Brazil. Electronic address: mpassere@usp.br.
authors.forename: Marisa
authors.initials: M
authors.lastname: Passarelli
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology*; D050197:Atherosclerosis / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D050171:Dyslipidemias / Q000503:physiopathology*; D017127:Glycation End Products, Advanced; D007249:Inflammation / Q000473:pathology*; D015227:Lipid Peroxidation; D008055:Lipids; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012084:Renin-Angiotensin System; D012709:Serum Albumin / Q000008:administration & dosage*; D000093423:Glycated Serum Albumin
chemical_list: D017127:Glycation End Products, Advanced; D008055:Lipids; D012709:Serum Albumin; D000093423:Glycated Serum Albumin
keywords: Advanced glycation; Atherosclerosis; Glycated albumin; Inflammation; Losartan; Oxidative stress