RAGE Mediates Cholesterol Efflux Impairment in Macrophages Caused by Human Advanced Glycated Albumin

• Published in: International journal of molecular sciences Vol. 21; no. 19; p. 7265
• Main Authors: Machado-Lima, Adriana, López-Díez, Raquel, Iborra, Rodrigo, Pinto, Raphael, Daffu, Gurdip, Shen, Xiaoping, Nakandakare, Edna, Machado, Ubiratan, Corrêa-Giannella, Maria, Schmidt, Ann, Passarelli, Marisa
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.10.2020; MDPI
• Subjects: Adult; Age; Albumin; Animals; Atherosclerosis; Bone marrow; Case-Control Studies; Cell Line; Cholesterol; Cholesterol, HDL - blood; Cholesterol, LDL - blood; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 1 - pathology; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; Female; Fibroblasts - cytology; Fibroblasts - drug effects; Fibroblasts - metabolism; Gene expression; Gene Expression Regulation; Glycated Hemoglobin A - genetics; Glycated Hemoglobin A - metabolism; Glycation End Products, Advanced - blood; Glycation End Products, Advanced - pharmacology; Health aspects; Homeostasis; Humans; Janus Kinase 2 - genetics; Janus Kinase 2 - metabolism; Kinases; Lipids; Macrophages; Macrophages - drug effects; Macrophages - metabolism; Macrophages - pathology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; NADPH Oxidase 4 - genetics; NADPH Oxidase 4 - metabolism; NF-kappa B p50 Subunit - genetics; NF-kappa B p50 Subunit - metabolism; Receptor for Advanced Glycation End Products - antagonists & inhibitors; Receptor for Advanced Glycation End Products - deficiency; Receptor for Advanced Glycation End Products - genetics; Receptor for Advanced Glycation End Products - metabolism; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Serum Albumin, Human - metabolism; Serum Albumin, Human - pharmacology; THP-1 Cells; Triglycerides - blood; Brazil; atherosclerosis; cholesterol; diabetes mellitus; RAGE; advanced glycation end products
• DOI: 10.3390/ijms21197265
• ISSN: 1422-0067; 1661-6596

We addressed the involvement of the receptor for advanced glycation end products (RAGE) in the impairment of the cellular cholesterol efflux elicited by glycated albumin. Albumin was isolated from type 1 (DM1) and type 2 (DM2) diabetes mellitus (HbA1c > 9%) and non-DM subjects (C). Moreover, albumin was glycated in vitro (AGE-albumin). Macrophages from Ager null and wild-type (WT) mice, or THP-1 transfected with siRNA-AGER, were treated with C, DM1, DM2, non-glycated or AGE-albumin. The cholesterol efflux was reduced in WT cells exposed to DM1 or DM2 albumin as compared to C, and the intracellular lipid content was increased. These events were not observed in Ager null cells, in which the cholesterol efflux and lipid staining were, respectively, higher and lower when compared to WT cells. In WT, Ager, Nox4 and Nfkb1, mRNA increased and Scd1 and Abcg1 diminished after treatment with DM1 and DM2 albumin. In Ager null cells treated with DM-albumin, Nox4, Scd1 and Nfkb1 were reduced and Jak2 and Abcg1 increased. In AGER-silenced THP-1, NOX4 and SCD1 mRNA were reduced and JAK2 and ABCG1 were increased even after treatment with AGE or DM-albumin. RAGE mediates the deleterious effects of AGE-albumin in macrophage cholesterol efflux.