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The crosstalk of ABCA1 and ANXA1: a potential mechanism for protection against atherosclerosis
Atherosclerosis, characterized by the formation of fat-laden plaques, is a chronic inflammatory disease. ABCA1 promotes cholesterol efflux, reduces cellular cholesterol accumulation, and regulates anti-inflammatory activities in an apoA-I- or ANXA1-dependent manner. The latter activity occurs by med...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487582/ https://www.ncbi.nlm.nih.gov/pubmed/32894039 http://dx.doi.org/10.1186/s10020-020-00213-y |
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author | Shen, Xin Zhang, Shun Guo, Zhu Xing, Dongming Chen, Wujun |
author_facet | Shen, Xin Zhang, Shun Guo, Zhu Xing, Dongming Chen, Wujun |
author_sort | Shen, Xin |
collection | PubMed |
description | Atherosclerosis, characterized by the formation of fat-laden plaques, is a chronic inflammatory disease. ABCA1 promotes cholesterol efflux, reduces cellular cholesterol accumulation, and regulates anti-inflammatory activities in an apoA-I- or ANXA1-dependent manner. The latter activity occurs by mediating the efflux of ANXA1, which plays a critical role in anti-inflammatory effects, cholesterol transport, exosome and microparticle secretion, and apoptotic cell clearance. ApoA-I increases ANXA1 expression via the ERK, p38MAPK, AKT, and PKC pathways. ApoA-I regulates the signaling pathways by binding to ABCA1, suggesting that apoA-I increases ANXA1 expression by binding to ABCA1. Furthermore, ANXA1 may increase ABCA1 expression. ANXA1 increases PPARγ expression by modulating STAT6 phosphorylation. PPARγ also increases ANXA1 expression by binding to the promoter of ANXA1. Therefore, ABCA1, PPARγ, and ANXA1 may form a feedback loop and regulate each other. Interestingly, the ANXA1 needs to be externalized to the cell membrane or secreted into the extracellular fluids to exert its anti-inflammatory properties. ABCA1 transports ANXA1 from the cytoplasm to the cell membrane by regulating lipidization and serine phosphorylation, thereby mediating ANXA1 efflux, likely by promoting microparticle and exosome release. The direct role of ABCA1 expression and ANXA1 release in atherosclerosis has been unclear. In this review, we focus on the role of ANXA1 in atheroprogression and its novel interaction with ABCA1, which may be useful for providing basic knowledge for the development of novel therapeutic targets for atherosclerosis and cardiovascular disease. |
format | Online Article Text |
id | pubmed-7487582 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-74875822020-09-15 The crosstalk of ABCA1 and ANXA1: a potential mechanism for protection against atherosclerosis Shen, Xin Zhang, Shun Guo, Zhu Xing, Dongming Chen, Wujun Mol Med Review Atherosclerosis, characterized by the formation of fat-laden plaques, is a chronic inflammatory disease. ABCA1 promotes cholesterol efflux, reduces cellular cholesterol accumulation, and regulates anti-inflammatory activities in an apoA-I- or ANXA1-dependent manner. The latter activity occurs by mediating the efflux of ANXA1, which plays a critical role in anti-inflammatory effects, cholesterol transport, exosome and microparticle secretion, and apoptotic cell clearance. ApoA-I increases ANXA1 expression via the ERK, p38MAPK, AKT, and PKC pathways. ApoA-I regulates the signaling pathways by binding to ABCA1, suggesting that apoA-I increases ANXA1 expression by binding to ABCA1. Furthermore, ANXA1 may increase ABCA1 expression. ANXA1 increases PPARγ expression by modulating STAT6 phosphorylation. PPARγ also increases ANXA1 expression by binding to the promoter of ANXA1. Therefore, ABCA1, PPARγ, and ANXA1 may form a feedback loop and regulate each other. Interestingly, the ANXA1 needs to be externalized to the cell membrane or secreted into the extracellular fluids to exert its anti-inflammatory properties. ABCA1 transports ANXA1 from the cytoplasm to the cell membrane by regulating lipidization and serine phosphorylation, thereby mediating ANXA1 efflux, likely by promoting microparticle and exosome release. The direct role of ABCA1 expression and ANXA1 release in atherosclerosis has been unclear. In this review, we focus on the role of ANXA1 in atheroprogression and its novel interaction with ABCA1, which may be useful for providing basic knowledge for the development of novel therapeutic targets for atherosclerosis and cardiovascular disease. BioMed Central 2020-09-07 /pmc/articles/PMC7487582/ /pubmed/32894039 http://dx.doi.org/10.1186/s10020-020-00213-y Text en © The Author(s) 2020 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/. |
spellingShingle | Review Shen, Xin Zhang, Shun Guo, Zhu Xing, Dongming Chen, Wujun The crosstalk of ABCA1 and ANXA1: a potential mechanism for protection against atherosclerosis |
title | The crosstalk of ABCA1 and ANXA1: a potential mechanism for protection against atherosclerosis |
title_full | The crosstalk of ABCA1 and ANXA1: a potential mechanism for protection against atherosclerosis |
title_fullStr | The crosstalk of ABCA1 and ANXA1: a potential mechanism for protection against atherosclerosis |
title_full_unstemmed | The crosstalk of ABCA1 and ANXA1: a potential mechanism for protection against atherosclerosis |
title_short | The crosstalk of ABCA1 and ANXA1: a potential mechanism for protection against atherosclerosis |
title_sort | crosstalk of abca1 and anxa1: a potential mechanism for protection against atherosclerosis |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487582/ https://www.ncbi.nlm.nih.gov/pubmed/32894039 http://dx.doi.org/10.1186/s10020-020-00213-y |
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