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Bilirubin ameliorates murine atherosclerosis through inhibiting cholesterol synthesis and reshaping the immune system
Atherosclerosis is a chronic inflammatory disease caused mainly by lipid accumulation and excessive inflammatory immune response. Although the lipid-lowering and cardioprotective properties of bilirubin, as well as the negative relationship between bilirubin and atherosclerosis, were well documented...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8722314/ https://www.ncbi.nlm.nih.gov/pubmed/34980160 http://dx.doi.org/10.1186/s12967-021-03207-4 |
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author | Wen, Guanmei Yao, Leyi Hao, Yali Wang, Jinheng Liu, Jinbao |
author_facet | Wen, Guanmei Yao, Leyi Hao, Yali Wang, Jinheng Liu, Jinbao |
author_sort | Wen, Guanmei |
collection | PubMed |
description | Atherosclerosis is a chronic inflammatory disease caused mainly by lipid accumulation and excessive inflammatory immune response. Although the lipid-lowering and cardioprotective properties of bilirubin, as well as the negative relationship between bilirubin and atherosclerosis, were well documented, it is not yet clear whether bilirubin can attenuate atherosclerosis in vivo. In this study, we investigated the role of bilirubin in improving atherosclerosis. We found that mildly elevated bilirubin significantly reduced the risk factors of atherosclerosis, such as plasma glucose, total cholesterol, and low-density lipoprotein cholesterol, and the formation of atherosclerotic plaques, liver total cholesterol, and cholesterol ester concentration in apolipoprotein E-deficient (ApoE(−/−)) mice fed a western-type (high fat) diet. It was further found that bilirubin could promote the degradation of 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGCR), a rate-limiting enzyme for endogenous cholesterol synthesis. Using mass cytometry-based high dimensional single cell analysis, we observed a decrease of natural killer cells and an increase of dendritic cells and myeloid-derived suppressor cells, which all are closely associated with atherosclerosis risk factors and contribute to the improvement of atherosclerosis, in ApoE(−/−) mice treated with bilirubin. By in-depth analysis, modulation of multiple spleen or peripheral blood T cell clusters exhibiting either positive or negative correlations with total cholesterol or low-density lipoprotein cholesterol was detected after bilirubin treatment. In this study, we demonstrate that bilirubin serves as a negative regulator of atherosclerosis and reduces atherosclerosis by inhibiting cholesterol synthesis and modulating the immune system. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-021-03207-4. |
format | Online Article Text |
id | pubmed-8722314 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-87223142022-01-06 Bilirubin ameliorates murine atherosclerosis through inhibiting cholesterol synthesis and reshaping the immune system Wen, Guanmei Yao, Leyi Hao, Yali Wang, Jinheng Liu, Jinbao J Transl Med Research Atherosclerosis is a chronic inflammatory disease caused mainly by lipid accumulation and excessive inflammatory immune response. Although the lipid-lowering and cardioprotective properties of bilirubin, as well as the negative relationship between bilirubin and atherosclerosis, were well documented, it is not yet clear whether bilirubin can attenuate atherosclerosis in vivo. In this study, we investigated the role of bilirubin in improving atherosclerosis. We found that mildly elevated bilirubin significantly reduced the risk factors of atherosclerosis, such as plasma glucose, total cholesterol, and low-density lipoprotein cholesterol, and the formation of atherosclerotic plaques, liver total cholesterol, and cholesterol ester concentration in apolipoprotein E-deficient (ApoE(−/−)) mice fed a western-type (high fat) diet. It was further found that bilirubin could promote the degradation of 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGCR), a rate-limiting enzyme for endogenous cholesterol synthesis. Using mass cytometry-based high dimensional single cell analysis, we observed a decrease of natural killer cells and an increase of dendritic cells and myeloid-derived suppressor cells, which all are closely associated with atherosclerosis risk factors and contribute to the improvement of atherosclerosis, in ApoE(−/−) mice treated with bilirubin. By in-depth analysis, modulation of multiple spleen or peripheral blood T cell clusters exhibiting either positive or negative correlations with total cholesterol or low-density lipoprotein cholesterol was detected after bilirubin treatment. In this study, we demonstrate that bilirubin serves as a negative regulator of atherosclerosis and reduces atherosclerosis by inhibiting cholesterol synthesis and modulating the immune system. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-021-03207-4. BioMed Central 2022-01-03 /pmc/articles/PMC8722314/ /pubmed/34980160 http://dx.doi.org/10.1186/s12967-021-03207-4 Text en © The Author(s) 2021 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 Wen, Guanmei Yao, Leyi Hao, Yali Wang, Jinheng Liu, Jinbao Bilirubin ameliorates murine atherosclerosis through inhibiting cholesterol synthesis and reshaping the immune system |
title | Bilirubin ameliorates murine atherosclerosis through inhibiting cholesterol synthesis and reshaping the immune system |
title_full | Bilirubin ameliorates murine atherosclerosis through inhibiting cholesterol synthesis and reshaping the immune system |
title_fullStr | Bilirubin ameliorates murine atherosclerosis through inhibiting cholesterol synthesis and reshaping the immune system |
title_full_unstemmed | Bilirubin ameliorates murine atherosclerosis through inhibiting cholesterol synthesis and reshaping the immune system |
title_short | Bilirubin ameliorates murine atherosclerosis through inhibiting cholesterol synthesis and reshaping the immune system |
title_sort | bilirubin ameliorates murine atherosclerosis through inhibiting cholesterol synthesis and reshaping the immune system |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8722314/ https://www.ncbi.nlm.nih.gov/pubmed/34980160 http://dx.doi.org/10.1186/s12967-021-03207-4 |
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