Advanced glycated albumin isolated from poorly controlled type 1 diabetes mellitus patients alters macrophage gene expression impairing ABCA‐1‐mediated reverse cholesterol transport

Machado-Lima, Adriana; Iborra, Rodrigo Tallada; Pinto, Raphael; Sartori, C.H.; Oliveira, Érika Renata Nascimento Cavalcanti de; Nakandakare, Edna Regina; Stefano, José Tadeu; Giannella-Neto, Daniel; Corrêa-Giannella, Maria Lúcia; Passarelli, Marisa

doi:10.1002/dmrr.2362

Cited by 45 publications

(47 citation statements)

References 39 publications

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“…Our group (Passarelli et al, ; Castilho et al, ; Machado‐Lima et al, ) and others (Isoda et al, ) have shown that AGE reduce ABCA‐1 protein content independent of changes in its mRNA expression. In fact, this reduction was observed in the present study in incubations with DM2‐HSA, which affected protein content without changes in mRNA levels.…”

Section: Discussionmentioning

confidence: 67%

In Type 2 Diabetes Mellitus Glycated Albumin Alters Macrophage Gene Expression Impairing ABCA1‐Mediated Cholesterol Efflux

Machado-Lima

Iborra

Pinto

et al. 2015

Journal Cellular Physiology

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Advanced glycation end products (AGE) are elevated in diabetes mellitus (DM) and predict the development of atherosclerosis. AGE-albumin induces oxidative stress, which is linked to a reduction in ABCA-1 and cholesterol efflux. We characterized the glycation level of human serum albumin (HSA) isolated from poorly controlled DM2 (n = 11) patients compared with that of control (C, n = 12) individuals and determined the mechanism by which DM2-HSA can interfere in macrophage lipid accumulation. The HSA glycation level was analyzed by MALDI/MS. Macrophages were treated for 18 h with C- or DM2-HSA to measure the (14) C-cholesterol efflux, the intracellular lipid accumulation and the cellular ABCA-1 protein content. Agilent arrays (44000 probes) were used to analyze gene expression, and the differentially expressed genes were validated by real-time RT-PCR. An increased mean mass was observed in DM2-HSA compared with C-HSA, reflecting the condensation of at least 5 units of glucose. The cholesterol efflux mediated by apo AI, HDL3 , and HDL2 was impaired in DM2-HSA-treated cells, which was related to greater intracellular lipid accumulation. DM2-HSA decreased Abcg1 mRNA expression by 26%. Abca1 mRNA was unchanged, although the final ABCA-1 protein content decreased. Compared with C-HAS-treated cells, NADPH oxidase 4 mRNA expression increased in cells after DM2-HSA treatment. Stearoyl-Coenzyme A desaturase 1, janus kinase 2, and low density lipoprotein receptor mRNAs were reduced by DM2-HSA. The level of glycation that occurs in vivo in DM2-HSA-treated cells selectively alters macrophage gene expression, impairing cholesterol efflux and eliciting intracellular lipid accumulation, which contribute to atherogenesis, in individuals with DM2.

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Section: Discussionmentioning

confidence: 67%

In Type 2 Diabetes Mellitus Glycated Albumin Alters Macrophage Gene Expression Impairing ABCA1‐Mediated Cholesterol Efflux

Machado-Lima

Iborra

Pinto

et al. 2015

Journal Cellular Physiology

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“…Advanced glycation is independently related to cardiovascular disease, by inducing oxidative and inflammatory stress and disturbing the flux of cholesterol from the artery wall to the liver in the reverse cholesterol transport pathway. This may contribute to atherogenesis in diabetes mellitus (DM), chronic kidney disease, and inflammatory diseases [49][50][51][52].…”

Section: Discussionmentioning

confidence: 99%

Advanced Glycated apoA-IV Loses Its Ability to Prevent the LPS-Induced Reduction in Cholesterol Efflux-Related Gene Expression in Macrophages

Okuda

Iborra

Pinto

et al. 2020

Mediators of Inflammation

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We addressed how advanced glycation (AGE) affects the ability of apoA-IV to impair inflammation and restore the expression of genes involved in cholesterol efflux in lipopolysaccharide- (LPS-) treated macrophages. Recombinant human apoA-IV was nonenzymatically glycated by incubation with glycolaldehyde (GAD), incubated with cholesterol-loaded bone marrow-derived macrophages (BMDMs), and then stimulated with LPS prior to measurement of proinflammatory cytokines by ELISA. Genes involved in cholesterol efflux were quantified by RT-qPCR, and cholesterol efflux was measured by liquid scintillation counting. Carboxymethyllysine (CML) and pyrraline (PYR) levels, determined by Liquid Chromatography-Mass Spectrometry (LC-MS/MS), were greater in AGE-modified apoA-IV (AGE-apoA-IV) compared to unmodified-apoA-IV. AGE-apoA-IV inhibited expression of interleukin 6 (Il6), TNF-alpha (Tnf), IL-1 beta (Il1b), toll-like receptor 4 (Tlr4), tumor necrosis factor receptor-associated factor 6 (Traf6), Janus kinase 2/signal transducer and activator of transcription 3 (Jak2/Stat3), nuclear factor kappa B (Nfkb), and AGE receptor 1 (Ddost) as well as IL-6 and TNF-alpha secretion. AGE-apoA-IV alone did not change cholesterol efflux or ABCA-1 levels but was unable to restore the LPS-induced reduction in expression of Abca1 and Abcg1. AGE-apoA-IV inhibited inflammation but lost its ability to counteract the LPS-induced changes in expression of genes involved in macrophage cholesterol efflux that may contribute to atherosclerosis.

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“…Cellular cholesterol efflux was also measured in a subgroup of volunteers (6 hypo, 6 controls and 7 hyper); J774 macrophages enriched with acetylated LDL and 14 C-cholesterol, using HDL as the cholesterol acceptor, as described earlier (Machado- Lima et al, 2013). Briefly, J774 macrophages were cultured in RPMI 1640 medium containing 10% fetal calf serum, penicillin and streptomycin and maintained in a 5% CO 2 incubator at 37°C.…”

Section: Cellular Cholesterol Effluxmentioning

confidence: 99%

Asymptomatic individuals with high HDL-C levels overexpress ABCA1 and ABCG1 and present miR-33a dysregulation in peripheral blood mononuclear cells

Scherrer

Zago

Parra

et al. 2015

Gene

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Advanced glycated albumin isolated from poorly controlled type 1 diabetes mellitus patients alters macrophage gene expression impairing ABCA‐1‐mediated reverse cholesterol transport

Abstract: (Carboxymethyl)lysine-modified albumin isolated from poorly controlled type 1 diabetic patients impairs ABCA-1-mediated reverse cholesterol transport and elicits intracellular lipid accumulation, possibly contributing to atherosclerosis.

Cited by 45 publications

References 39 publications

In Type 2 Diabetes Mellitus Glycated Albumin Alters Macrophage Gene Expression Impairing ABCA1‐Mediated Cholesterol Efflux

In Type 2 Diabetes Mellitus Glycated Albumin Alters Macrophage Gene Expression Impairing ABCA1‐Mediated Cholesterol Efflux

Advanced Glycated apoA-IV Loses Its Ability to Prevent the LPS-Induced Reduction in Cholesterol Efflux-Related Gene Expression in Macrophages

Asymptomatic individuals with high HDL-C levels overexpress ABCA1 and ABCG1 and present miR-33a dysregulation in peripheral blood mononuclear cells

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