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

International Journal of Molecular Sciences

Xiaoping Shen¹  Raquel López-Díez¹  Gurdip Daffu¹  AnnMarie Schmidt¹  MariaLucia Cardillo Corrêa-Giannella²  Marisa Passarelli³  Adriana Machado-Lima³  Raphaelde Souza Pinto³  EdnaRegina Nakandakare³  RodrigoTallada Iborra³  UbiratanFabres Machado⁴ 

[1] Department of Medicine, Diabetes Research Program, New York University Langone Health, New York, NY 10016, USA;Laboratório de Carboidratos e Radioimunoensaio (LIM 18), Hospital das Clínicas (HCFMUSP), Faculdade de Medicina da Universidade de São Paulo, São Paulo CEP 01246-000, Brazil;Laboratório de Lípides (LIM 10), Hospital das Clínicas (HCFMUSP), Faculdade de Medicina da Universidade de São Paulo, São Paulo CEP 01246-000, Brazil;Laboratório de Metabolismo e Endocrinologia, Instituto de Ciências Biomédicas da Universidade de São Paulo, São Paulo CEP 05508-000, Brazil;

关键词: diabetes mellitus;    advanced glycation end products;    cholesterol;    RAGE;    atherosclerosis;   

DOI  :  10.3390/ijms21197265

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown