DHX9 Strengthens Atherosclerosis Progression By Promoting Inflammation in Macrophages
Atherosclerosis (AS) is the main cause of cerebrovascular diseases, and macrophages play important roles in atherosclerosis. DExH-Box helicase 9 (DHX9), as a member of DExD/H-box RNA helicase superfamily II, is identified as an autoantigen in the sera of systemic lupus erythematosus patients to trig...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer US
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10567826/ https://www.ncbi.nlm.nih.gov/pubmed/37326773 http://dx.doi.org/10.1007/s10753-023-01836-z |
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author | Huangfu, Ning Ma, Hongchuang Tian, Mengyun Zhang, Jie Wang, Yong Li, Zhenwei Chen, Xiaomin Cui, Hanbin |
author_facet | Huangfu, Ning Ma, Hongchuang Tian, Mengyun Zhang, Jie Wang, Yong Li, Zhenwei Chen, Xiaomin Cui, Hanbin |
author_sort | Huangfu, Ning |
collection | PubMed |
description | Atherosclerosis (AS) is the main cause of cerebrovascular diseases, and macrophages play important roles in atherosclerosis. DExH-Box helicase 9 (DHX9), as a member of DExD/H-box RNA helicase superfamily II, is identified as an autoantigen in the sera of systemic lupus erythematosus patients to trigger inflammation. The aim of this study was to investigate whether DHX9 is involved in AS development, especially in macrophages-mediated-inflammatory responses. We find that DHX9 expression is significantly increased in oxLDL or interferon-γ-treated macrophages and peripheral blood mononuclear cells (PBMCs) from patients with coronary artery disease (CAD). Knockdown of DHX9 inhibits lipid uptake and pro-inflammatory factors expression in macrophages, and ameliorates TNF-α-mediated monocyte adhesion capacity. Furthermore, we find that oxLDL stimulation promotes DHX9 interaction with p65 in macrophages, and further enhances the transcriptional activity of DHX9-p65-RNA Polymerase II complex to produce inflammatory factors. Moreover, using ApoE -/- mice fed with western diet to establish AS model, we find that knockdown of DHX9 mediated by adeno-associated virus-Sh-DHX9 through tail vein injection evidently alleviates AS progression in vivo. Finally, we also find that knockdown of DHX9 inhibits p65 activation, inflammatory factors expression, and the transcriptional activity of p65-RNA Polymerase II complex in PBMCs from patients with CAD. Overall, these results indicate that DHX9 promotes AS progression by enhancing inflammation in macrophages, and suggest DHX9 as a potential target for developing therapeutic drug. |
format | Online Article Text |
id | pubmed-10567826 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-105678262023-10-13 DHX9 Strengthens Atherosclerosis Progression By Promoting Inflammation in Macrophages Huangfu, Ning Ma, Hongchuang Tian, Mengyun Zhang, Jie Wang, Yong Li, Zhenwei Chen, Xiaomin Cui, Hanbin Inflammation Research Atherosclerosis (AS) is the main cause of cerebrovascular diseases, and macrophages play important roles in atherosclerosis. DExH-Box helicase 9 (DHX9), as a member of DExD/H-box RNA helicase superfamily II, is identified as an autoantigen in the sera of systemic lupus erythematosus patients to trigger inflammation. The aim of this study was to investigate whether DHX9 is involved in AS development, especially in macrophages-mediated-inflammatory responses. We find that DHX9 expression is significantly increased in oxLDL or interferon-γ-treated macrophages and peripheral blood mononuclear cells (PBMCs) from patients with coronary artery disease (CAD). Knockdown of DHX9 inhibits lipid uptake and pro-inflammatory factors expression in macrophages, and ameliorates TNF-α-mediated monocyte adhesion capacity. Furthermore, we find that oxLDL stimulation promotes DHX9 interaction with p65 in macrophages, and further enhances the transcriptional activity of DHX9-p65-RNA Polymerase II complex to produce inflammatory factors. Moreover, using ApoE -/- mice fed with western diet to establish AS model, we find that knockdown of DHX9 mediated by adeno-associated virus-Sh-DHX9 through tail vein injection evidently alleviates AS progression in vivo. Finally, we also find that knockdown of DHX9 inhibits p65 activation, inflammatory factors expression, and the transcriptional activity of p65-RNA Polymerase II complex in PBMCs from patients with CAD. Overall, these results indicate that DHX9 promotes AS progression by enhancing inflammation in macrophages, and suggest DHX9 as a potential target for developing therapeutic drug. Springer US 2023-06-16 2023 /pmc/articles/PMC10567826/ /pubmed/37326773 http://dx.doi.org/10.1007/s10753-023-01836-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This 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/) . |
spellingShingle | Research Huangfu, Ning Ma, Hongchuang Tian, Mengyun Zhang, Jie Wang, Yong Li, Zhenwei Chen, Xiaomin Cui, Hanbin DHX9 Strengthens Atherosclerosis Progression By Promoting Inflammation in Macrophages |
title | DHX9 Strengthens Atherosclerosis Progression By Promoting Inflammation in Macrophages |
title_full | DHX9 Strengthens Atherosclerosis Progression By Promoting Inflammation in Macrophages |
title_fullStr | DHX9 Strengthens Atherosclerosis Progression By Promoting Inflammation in Macrophages |
title_full_unstemmed | DHX9 Strengthens Atherosclerosis Progression By Promoting Inflammation in Macrophages |
title_short | DHX9 Strengthens Atherosclerosis Progression By Promoting Inflammation in Macrophages |
title_sort | dhx9 strengthens atherosclerosis progression by promoting inflammation in macrophages |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10567826/ https://www.ncbi.nlm.nih.gov/pubmed/37326773 http://dx.doi.org/10.1007/s10753-023-01836-z |
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