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Article

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

by
Adriana Machado-Lima
1,2,
Raquel López-Díez
3,
Rodrigo Tallada Iborra
1,2,
Raphael de Souza Pinto
1,4,
Gurdip Daffu
3,
Xiaoping Shen
3,
Edna Regina Nakandakare
1,
Ubiratan Fabres Machado
5,
Maria Lucia Cardillo Corrêa-Giannella
6,7,
Ann Marie Schmidt
3 and
Marisa Passarelli
1,7,*,†
1
Laboratório de Lípides (LIM 10), Hospital das Clínicas (HCFMUSP), Faculdade de Medicina da Universidade de São Paulo, São Paulo CEP 01246-000, Brazil
2
Programa de Pós-Graduação em Ciências do Envelhecimento, Universidade São Judas Tadeu, São Paulo CEP 03166-000, Brazil
3
Department of Medicine, Diabetes Research Program, New York University Langone Health, New York, NY 10016, USA
4
Curso de Biomedicina, Centro Universitário CESMAC, Maceió, Alagoas CEP 57051-160, Brazil
5
Laboratório de Metabolismo e Endocrinologia, Instituto de Ciências Biomédicas da Universidade de São Paulo, São Paulo CEP 05508-000, Brazil
6
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
7
Programa de Pós-Graduação em Medicina, Universidade Nove de Julho, São Paulo CEP 01225-000, Brazil
*
Author to whom correspondence should be addressed.
†
Present address: Marisa Passarelli, Laboratório de Lípides (LIM 10), Hospital das Clínicas (HCFMUSP), Faculdade de Medicina da Universidade de São Paulo, Brazil. Av Dr. Arnaldo 455 sala 3305, São Paulo CEP 01246-000, Brazil.
Int. J. Mol. Sci. 2020, 21(19), 7265; https://doi.org/10.3390/ijms21197265
Submission received: 1 June 2020 / Revised: 26 June 2020 / Accepted: 17 July 2020 / Published: 1 October 2020
(This article belongs to the Section Molecular Endocrinology and Metabolism)
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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.
Keywords: diabetes mellitus; advanced glycation end products; cholesterol; RAGE; atherosclerosis diabetes mellitus; advanced glycation end products; cholesterol; RAGE; atherosclerosis

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MDPI and ACS Style

Machado-Lima, A.; López-Díez, R.; Iborra, R.T.; Pinto, R.d.S.; Daffu, G.; Shen, X.; Nakandakare, E.R.; Machado, U.F.; Corrêa-Giannella, M.L.C.; Schmidt, A.M.; et al. RAGE Mediates Cholesterol Efflux Impairment in Macrophages Caused by Human Advanced Glycated Albumin. Int. J. Mol. Sci. 2020, 21, 7265. https://doi.org/10.3390/ijms21197265

AMA Style

Machado-Lima A, López-Díez R, Iborra RT, Pinto RdS, Daffu G, Shen X, Nakandakare ER, Machado UF, Corrêa-Giannella MLC, Schmidt AM, et al. RAGE Mediates Cholesterol Efflux Impairment in Macrophages Caused by Human Advanced Glycated Albumin. International Journal of Molecular Sciences. 2020; 21(19):7265. https://doi.org/10.3390/ijms21197265

Chicago/Turabian Style

Machado-Lima, Adriana, Raquel López-Díez, Rodrigo Tallada Iborra, Raphael de Souza Pinto, Gurdip Daffu, Xiaoping Shen, Edna Regina Nakandakare, Ubiratan Fabres Machado, Maria Lucia Cardillo Corrêa-Giannella, Ann Marie Schmidt, and et al. 2020. "RAGE Mediates Cholesterol Efflux Impairment in Macrophages Caused by Human Advanced Glycated Albumin" International Journal of Molecular Sciences 21, no. 19: 7265. https://doi.org/10.3390/ijms21197265

APA Style

Machado-Lima, A., López-Díez, R., Iborra, R. T., Pinto, R. d. S., Daffu, G., Shen, X., Nakandakare, E. R., Machado, U. F., Corrêa-Giannella, M. L. C., Schmidt, A. M., & Passarelli, M. (2020). RAGE Mediates Cholesterol Efflux Impairment in Macrophages Caused by Human Advanced Glycated Albumin. International Journal of Molecular Sciences, 21(19), 7265. https://doi.org/10.3390/ijms21197265

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