Advanced glycated albumin isolated from poorly controlled type 1 diabetes mellitus patients alters macrophage gene expression impairing ABCA-1-mediated reverse cholesterol transport

• Published in: Diabetes/metabolism research and reviews Vol. 29; no. 1; pp. 66 - 76
• Main Authors: Machado-Lima, Adriana, Iborra, Rodrigo T., Pinto, Raphael S., Sartori, Camila H., Oliveira, Erika R., Nakandakare, Edna R., Stefano, José T., Giannella-Neto, Daniel, Corrêa-Giannella, Maria Lucia C., Passarelli, Marisa
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.01.2013; Wiley Subscription Services, Inc
• Subjects: ABCA-1; Adult; advanced glycation end product; albumin; ATP Binding Cassette Transporter 1; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - metabolism; Biological Transport - physiology; Cholesterol - metabolism; diabetes; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - metabolism; Female; Gene Expression; Glycation End Products, Advanced - genetics; Glycation End Products, Advanced - metabolism; Glycosylation; Humans; Lipoproteins, HDL - genetics; Lipoproteins, HDL - metabolism; Macrophages - metabolism; Male; reverse cholesterol transport; Serum Albumin - genetics; Serum Albumin - metabolism
• ISSN: 1520-7552; 1520-7560
• DOI: 10.1002/dmrr.2362

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). 14C‐cholesterol‐labelled J774 macrophages treated with albumin were employed to measure cholesterol efflux mediated by apo A‐I, HDL3 or HDL2, 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 HDL2‐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. Copyright © 2012 John Wiley & Sons, Ltd.