PMID- 32410861 OWN - NLM STAT- MEDLINE DCOM- 20210709 LR - 20210709 IS - 1466-1861 (Electronic) IS - 0962-9351 (Print) IS - 0962-9351 (Linking) VI - 2020 DP - 2020 TI - Advanced Glycated apoA-IV Loses Its Ability to Prevent the LPS-Induced Reduction in Cholesterol Efflux-Related Gene Expression in Macrophages. PG - 6515401 LID - 10.1155/2020/6515401 [doi] LID - 6515401 AB - 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. CI - Copyright (c) 2020 Ligia Shimabukuro Okuda et al. FAU - Shimabukuro Okuda, Ligia AU - Shimabukuro Okuda L AUID- ORCID: 0000-0003-0356-1543 AD - Laboratorio de Lipides (LIM 10), Hospital das Clinicas (HCFMUSP), Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil. FAU - Tallada Iborra, Rodrigo AU - Tallada Iborra R AD - Laboratorio de Lipides (LIM 10), Hospital das Clinicas (HCFMUSP), Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil. AD - Universidade Sao Judas Tadeu, Sao Paulo, Brazil. FAU - Ramos Pinto, Paula AU - Ramos Pinto P AD - Laboratorio de Lipides (LIM 10), Hospital das Clinicas (HCFMUSP), Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil. FAU - Fabres Machado, Ubiratan AU - Fabres Machado U AUID- ORCID: 0000-0002-8237-2435 AD - Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil. FAU - Correa-Giannella, Maria Lucia AU - Correa-Giannella ML AD - Laboratorio de Carboidratos e Radioimunoensaio (LIM 18), Hospital das Clinicas (HCFMUSP), Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil. AD - Programa de Pos-Graduacao em Medicina, Universidade Nove de Julho, Sao Paulo, Brazil. FAU - Pickford, Russell AU - Pickford R AD - Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, Australia. FAU - Woods, Tom AU - Woods T AD - School of Chemical Sciences, University of Auckland, Auckland, New Zealand. FAU - Brimble, Margaret Anne AU - Brimble MA AD - School of Chemical Sciences, University of Auckland, Auckland, New Zealand. FAU - Rye, Kerry-Anne AU - Rye KA AD - Lipid Research Group, School of Medical Sciences, University of New South Wales, Sydney, Australia. FAU - Passarelli, Marisa AU - Passarelli M AUID- ORCID: 0000-0002-9249-4698 AD - Laboratorio de Lipides (LIM 10), Hospital das Clinicas (HCFMUSP), Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil. AD - Programa de Pos-Graduacao em Medicina, Universidade Nove de Julho, Sao Paulo, Brazil. LA - eng PT - Journal Article DEP - 20200114 PL - United States TA - Mediators Inflamm JT - Mediators of inflammation JID - 9209001 RN - 0 (Apolipoproteins A) RN - 0 (Glycation End Products, Advanced) RN - 0 (Lipopolysaccharides) RN - 0 (Recombinant Proteins) RN - 0 (apolipoprotein A-IV) RN - 97C5T2UQ7J (Cholesterol) RN - GO1N1ZPR3B (Acetaldehyde) RN - W0A0XPU08U (glycolaldehyde) SB - IM MH - Acetaldehyde/analogs & derivatives/chemistry MH - Animals MH - Apolipoproteins A/chemistry/*metabolism MH - Bone Marrow Cells/cytology MH - Cholesterol/*metabolism MH - Chromatography, Liquid MH - Gene Expression Profiling MH - *Glycation End Products, Advanced MH - Humans MH - Inflammation MH - Lipopolysaccharides/*chemistry MH - Macrophages/*metabolism MH - Mass Spectrometry MH - Mice MH - Mice, Inbred C57BL MH - Oxidative Stress MH - Recombinant Proteins/chemistry PMC - PMC7201780 COIS- The authors declare that there is no conflict of interest regarding the publication of this paper. EDAT- 2020/05/16 06:00 MHDA- 2021/07/10 06:00 PMCR- 2020/01/14 CRDT- 2020/05/16 06:00 PHST- 2019/10/18 00:00 [received] PHST- 2019/12/06 00:00 [revised] PHST- 2019/12/21 00:00 [accepted] PHST- 2020/05/16 06:00 [entrez] PHST- 2020/05/16 06:00 [pubmed] PHST- 2021/07/10 06:00 [medline] PHST- 2020/01/14 00:00 [pmc-release] AID - 10.1155/2020/6515401 [doi] PST - epublish SO - Mediators Inflamm. 2020 Jan 14;2020:6515401. doi: 10.1155/2020/6515401. eCollection 2020.