albumin - publications
Advanced glycated albumin isolated from poorly controlled type 1 diabetes mellitus patients alters macrophage gene expression impairing ABCA-1 mediated reverse cholesterol transport.
Diabetes Metab Res Rev. 2012 Sep 26;
Authors: Machado-Lima A, Iborra RT, Pinto RS, Sartori CH, Oliveira ER, Nakandakare ER, Stefano JT, Giannella-Neto D, Corrêa-Giannella ML, Passarelli M
BACKGROUND: To evaluate 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 controlsubjects (n = 12) and from patients with poorly controlled Type 1 diabetes mellitus (n = 13). (14) C-cholesterol-labeled 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 analyze gene expression. Several differentially expressed genes were validated by real-time RT-PCR using TaqMan Two Step RT-PCR. RESULTS: Levels of glycated- and (carboxymethyl)lysine-modified albumin were higher in diabetic patients than in control subjects. Apo A-I and HDL(2) -mediated cellular cholesterol efflux was impaired in macrophages treated with albumin from diabetic patients in comparison to 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 to 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 extracted 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.
PMID: 23015358 [PubMed - as supplied by publisher]