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

Author(s):Show less -

Machado-Lima, Adriana ^{[1, 2]} ; Lopez-Diez, Raquel ^[3] ; Iborra, Rodrigo Tallada ^{[1, 2]} ; Pinto, Raphael de Souza ^{[1, 4]} ; Daffu, Gurdip ^[3] ; Shen, Xiaoping ^[3] ; Nakandakare, Edna Regina ^[1] ; Machado, Ubiratan Fabres ^[5] ; Correa-Giannella, Maria Lucia Cardillo ^{[6, 7]} ; Schmidt, Ann Marie ^[3] ; Passarelli, Marisa ^{[1, 6]}

Affiliation

^[1] Univ Sao Paulo, Lab Lipides LIM 10, Hosp Clin HCFMUSP, Fac Med, Av Dr Arnaldo 455 Sala 3305, BR-01246000 Sao Paulo - Brazil

^[2] Univ Sao Judas Tadeu, Programa Posgrad Ciencias Envelhecimento, BR-03166000 Sao Paulo - Brazil

^[3] New York Univ Langone Hlth, Dept Med, Diabet Res Program, New York, NY 10016 - USA

^[4] Ctr Univ CESMAC, Curso Biomed, BR-57051160 Maceio, Alagoas - Brazil

^[5] Univ Sao Paulo, Lab Metab & Endocrinol, Inst Ciencias Biomed, BR-05508000 Sao Paulo - Brazil

^[6] Univ Nove Julho, Programa Posgrad Med, BR-01225000 Sao Paulo - Brazil

^[7] Univ Sao Paulo, Lab Carboidratos & Radioimunoensaio LIM 18, Hosp Clin HCFMUSP, Fac Med, BR-01246000 Sao Paulo - Brazil

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 21, n. 19 OCT 2020.
• Web of Science Citations: 0

Abstract

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. (AU)

• FAPESP's process: 12/19112-0 - Involvement of the RAGE/AGE axis in macrophage lipid accumulation induced by human advanced glycated albumin - contribution of glycemic control in diabetes mellitus.
• Grantee: Adriana Machado Saldiba de Lima
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 15/21072-5 - Influence of the glycemic control and nephropathy stage on the reverse cholesterol transport in Diabetes mellitus: role of metabolic memory induced by advanced glycated albumin
• Grantee: Marisa Passarelli
• Support type: Regular Research Grants
• FAPESP's process: 13/06800-9 - Involvement of the RAGE/AGE axis in macrophage lipid accumulation induced by human advanced glycated albumin
• Grantee: Adriana Machado Saldiba de Lima
• Support type: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 18/00172-0 - Advanced glycation products, endoplasmic reticulum stress and the modulation of the reverse cholesterol transport in human arteries with different levels Atherosclerotic lesion
• Grantee: Raphael de Souza Pinto
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 13/26256-1 - Intracellular trafficking of HDL receptor - ABCA-1 - in macrophages treated with advanced glycated albumin: influence of glycemic control in reverse cholesterol transport
• Grantee: Rodrigo Tallada Iborra
• Support type: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 12/12088-7 - Glycemic control and the removal of macrophage cholesterol by ABCA-1: role of modified albumin by advanced glycation
• Grantee: Rodrigo Tallada Iborra
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 14/05951-6 - Involvement of the RAGE/AGE axis in macrophage lipid accumulation induced by human advanced glycated albumin
• Grantee: Adriana Machado Saldiba de Lima
• Support type: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 16/15603-0 - Unraveling mechanisms of glycemic control and chronic complications of Diabetes mellitus: contributions to human health
• Grantee: Ubiratan Fabres Machado
• Support type: Research Projects - Thematic Grants