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...

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Autores principales: Huangfu, Ning, Ma, Hongchuang, Tian, Mengyun, Zhang, Jie, Wang, Yong, Li, Zhenwei, Chen, Xiaomin, Cui, Hanbin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2023
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.
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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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