Advanced glycated albumin isolated from poorly controlled type 1 diabetes mellitus patients alters macrophage gene expression impairing ABCA-1-mediated reverse cholesterol transport
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 w...
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Published in | Diabetes/metabolism research and reviews Vol. 29; no. 1; pp. 66 - 76 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Blackwell Publishing Ltd
01.01.2013
Wiley Subscription Services, Inc |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ark:/67375/WNG-T6NHSV1Q-4 ArticleID:DMRR2362 istex:61B5177521FF11540D9B93B86638B61CE2B21D69 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1520-7552 1520-7560 |
DOI: | 10.1002/dmrr.2362 |