Persistent Effect of Advanced Glycated Albumin Driving Inflammation and Disturbances in Cholesterol Efflux in Macrophages

Nutrients

Maria Lúcia Cardillo Côrrea-Giannella¹  Raphael de Souza Pinto²  Aécio Lopes de Araújo Lira²  Edna Regina Nakandakare²  Marisa Passarelli²  Adriana Machado-Lima²  Lígia Shimabukuro Okuda²  Rodrigo Tallada Iborra²  Monique de Fátima Mello Santana²  Carlos André Minanni² 

[1] Laboratório de Carboidratos e Radioimunoensaio (LIM-18), Hospital das Clínicas (HCFMUSP) da Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-000, Brazil;Laboratório de Lípides (LIM-10), Hospital das Clínicas (HCFMUSP) da Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-000, Brazil;

关键词: advanced glycated albumin;    diabetes mellitus;    cholesterol efflux;    ABCA-1;    inflammation;    atherosclerosis;   

DOI  :  10.3390/nu13103633

来源: DOAJ

【 摘 要 】

Advanced glycated albumin (AGE-albumin) impairs cholesterol efflux and contributes to inflammation in macrophages. The current study evaluated: (1) the persistence of the deleterious effect of AGE-albumin in cholesterol efflux and in inflammation, and (2) how metabolic control in diabetes mellitus (DM) contributes to attenuate the deleterious role of AGE-albumin in macrophage cholesterol homeostasis. Methods: AGE-albumin was produced in vitro or isolated from uncontrolled DM subjects’ serum before (bGC) and after improved glycemic control (aGC). Albumin samples were incubated with bone marrow-derived macrophages and ¹⁴C-cholesterol efflux or LPS- induced cytokine secretion were determined immediately, or after cell resting in culture media alone. The ABCA-1 degradation rate was determined after cell incubation with cycloheximide, and ABCA1 protein level by immunoblot. Oil Red O staining was used to assess intracellular lipid accumulation. Results: A persistent effect of AGE-albumin was observed in macrophages in terms of the secretion of inflammatory cytokines and reduced cholesterol efflux. HDL-mediated ¹⁴C-cholesterol efflux was at least two times higher in macrophages treated with aCG-albumin as compared to bGC-albumin, and intracellular lipid content was significantly reduced in aGC-albumin-treated cells. As compared to bGC-albumin, the ABCA-1 protein content in whole cell bulk was 94% higher in aCG-albumin. A 20% increased ABCA-1 decay rate was observed in macrophages treated with albumin from poorly controlled DM. AGE-albumin has a persistent deleterious effect on macrophage lipid homeostasis and inflammation. The reduction of AGEs in albumin ameliorates cholesterol efflux.

【 授权许可】

Unknown