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Atheroprotective mechanism by which folic acid regulates monocyte subsets and function through DNA methylation
BACKGROUND: Recent studies have suggested that folic acid can restore abnormal DNA methylation and monocyte subset shifts caused by hyperhomocysteinemia (HHcy) and hyperlipidemia (HL). However, the exact mechanism of action is still not fully understood. In this study, we further investigated the re...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8887029/ https://www.ncbi.nlm.nih.gov/pubmed/35227297 http://dx.doi.org/10.1186/s13148-022-01248-0 |
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author | Xiang, Yang Liang, Bin Zhang, Xiaokang Qiu, Xueping Deng, Qianyun Yu, Li Yu, Hong Lu, Zhibing Zheng, Fang |
author_facet | Xiang, Yang Liang, Bin Zhang, Xiaokang Qiu, Xueping Deng, Qianyun Yu, Li Yu, Hong Lu, Zhibing Zheng, Fang |
author_sort | Xiang, Yang |
collection | PubMed |
description | BACKGROUND: Recent studies have suggested that folic acid can restore abnormal DNA methylation and monocyte subset shifts caused by hyperhomocysteinemia (HHcy) and hyperlipidemia (HL). However, the exact mechanism of action is still not fully understood. In this study, we further investigated the reversal effect and underlying mechanism of folic acid on the shift in monocyte subsets induced by aberrant lipids and Hcy metabolism via DNA methylation in vitro and in vivo. RESULTS: Our results showed that intermediate monocytes were significantly increased but had the lowest global 5-methylcytosine (5-mC) levels in coronary artery disease (CAD) patients, which might lead to a decrease in the global 5-mC levels of peripheral blood leukocytes (PBLs). We also discovered that ARID5B might mediate the increased proportion of intermediate monocytes, as this factor was related to the proportion of monocyte subsets and the expression of CCR2. The expression of ARID5B was inversely associated with the hypermethylated cg25953130 CpG site, which was induced by HL and HHcy. ARID5B could also regulate monocyte CCR2, MCP-1, and TNF-α expression, adhesion and migration, macrophage polarization, and monocyte/macrophage apoptosis, which might explain the regulatory effect of ARID5B on monocyte subset shifting. Folic acid reversed HL- and HHcy-mediated aberrant global and cg25953130 DNA methylation, reduced the proportion of intermediate monocytes, and inhibited the formation of atherosclerotic plaques. CONCLUSION: Folic acid plays a protective role against atherosclerosis through the regulation of DNA methylation, ARID5B expression, and monocyte subsets. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13148-022-01248-0. |
format | Online Article Text |
id | pubmed-8887029 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-88870292022-03-17 Atheroprotective mechanism by which folic acid regulates monocyte subsets and function through DNA methylation Xiang, Yang Liang, Bin Zhang, Xiaokang Qiu, Xueping Deng, Qianyun Yu, Li Yu, Hong Lu, Zhibing Zheng, Fang Clin Epigenetics Research BACKGROUND: Recent studies have suggested that folic acid can restore abnormal DNA methylation and monocyte subset shifts caused by hyperhomocysteinemia (HHcy) and hyperlipidemia (HL). However, the exact mechanism of action is still not fully understood. In this study, we further investigated the reversal effect and underlying mechanism of folic acid on the shift in monocyte subsets induced by aberrant lipids and Hcy metabolism via DNA methylation in vitro and in vivo. RESULTS: Our results showed that intermediate monocytes were significantly increased but had the lowest global 5-methylcytosine (5-mC) levels in coronary artery disease (CAD) patients, which might lead to a decrease in the global 5-mC levels of peripheral blood leukocytes (PBLs). We also discovered that ARID5B might mediate the increased proportion of intermediate monocytes, as this factor was related to the proportion of monocyte subsets and the expression of CCR2. The expression of ARID5B was inversely associated with the hypermethylated cg25953130 CpG site, which was induced by HL and HHcy. ARID5B could also regulate monocyte CCR2, MCP-1, and TNF-α expression, adhesion and migration, macrophage polarization, and monocyte/macrophage apoptosis, which might explain the regulatory effect of ARID5B on monocyte subset shifting. Folic acid reversed HL- and HHcy-mediated aberrant global and cg25953130 DNA methylation, reduced the proportion of intermediate monocytes, and inhibited the formation of atherosclerotic plaques. CONCLUSION: Folic acid plays a protective role against atherosclerosis through the regulation of DNA methylation, ARID5B expression, and monocyte subsets. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13148-022-01248-0. BioMed Central 2022-02-28 /pmc/articles/PMC8887029/ /pubmed/35227297 http://dx.doi.org/10.1186/s13148-022-01248-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Xiang, Yang Liang, Bin Zhang, Xiaokang Qiu, Xueping Deng, Qianyun Yu, Li Yu, Hong Lu, Zhibing Zheng, Fang Atheroprotective mechanism by which folic acid regulates monocyte subsets and function through DNA methylation |
title | Atheroprotective mechanism by which folic acid regulates monocyte subsets and function through DNA methylation |
title_full | Atheroprotective mechanism by which folic acid regulates monocyte subsets and function through DNA methylation |
title_fullStr | Atheroprotective mechanism by which folic acid regulates monocyte subsets and function through DNA methylation |
title_full_unstemmed | Atheroprotective mechanism by which folic acid regulates monocyte subsets and function through DNA methylation |
title_short | Atheroprotective mechanism by which folic acid regulates monocyte subsets and function through DNA methylation |
title_sort | atheroprotective mechanism by which folic acid regulates monocyte subsets and function through dna methylation |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8887029/ https://www.ncbi.nlm.nih.gov/pubmed/35227297 http://dx.doi.org/10.1186/s13148-022-01248-0 |
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