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Neuraminidase 1 Exacerbating Aortic Dissection by Governing a Pro-Inflammatory Program in Macrophages
Inflammation plays an important role in aortic dissection (AD). Macrophages are critically involved in the inflammation after aortic injury. Neuraminidases (NEUs) are a family of enzymes that catalyze the cleavage of terminal sialic acids from glycoproteins or glycolipids, which is emerging as a reg...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8639188/ https://www.ncbi.nlm.nih.gov/pubmed/34869700 http://dx.doi.org/10.3389/fcvm.2021.788645 |
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author | Wang, Qian Chen, Zhaoyang Peng, Xiaoping Zheng, Zeqi Le, Aiping Guo, Junjie Ma, Leilei Shi, Hongtao Yao, Kang Zhang, Shuning Zheng, Zhenzhong Zhu, Jianbing |
author_facet | Wang, Qian Chen, Zhaoyang Peng, Xiaoping Zheng, Zeqi Le, Aiping Guo, Junjie Ma, Leilei Shi, Hongtao Yao, Kang Zhang, Shuning Zheng, Zhenzhong Zhu, Jianbing |
author_sort | Wang, Qian |
collection | PubMed |
description | Inflammation plays an important role in aortic dissection (AD). Macrophages are critically involved in the inflammation after aortic injury. Neuraminidases (NEUs) are a family of enzymes that catalyze the cleavage of terminal sialic acids from glycoproteins or glycolipids, which is emerging as a regulator of macrophage-associated immune responses. However, the role of neuraminidase 1 (NEU1) in pathological vascular remodeling of AD remains largely unknown. This study sought to characterize the role and identify the potential mechanism of NEU1 in pathological aortic degeneration. After β-aminopropionitrile monofumarate (BAPN) administration, NEU1 elevated significantly in the lesion zone of the aorta. Global or macrophage-specific NEU1 knockout (NEU1 CKO) mice had no baseline aortic defects but manifested improved aorta function, and decreased mortality due to aortic rupture. Improved outcomes in NEU1 CKO mice subjected to BAPN treatment were associated with the ameliorated vascular inflammation, lowered apoptosis, decreased reactive oxygen species production, mitigated extracellular matrix degradation, and improved M2 macrophage polarization. Furthermore, macrophages sorted from the aorta of NEU1 CKO mice displayed a significant increase of M2 macrophage markers and a marked decrease of M1 macrophage markers compared with the controls. To summarize, the present study demonstrated that macrophage-derived NEU1 is critical for vascular homeostasis. NEU1 exacerbates BAPN-induced pathological vascular remodeling. NEU1 may therefore represent a potential therapeutic target for the treatment of AD. |
format | Online Article Text |
id | pubmed-8639188 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86391882021-12-03 Neuraminidase 1 Exacerbating Aortic Dissection by Governing a Pro-Inflammatory Program in Macrophages Wang, Qian Chen, Zhaoyang Peng, Xiaoping Zheng, Zeqi Le, Aiping Guo, Junjie Ma, Leilei Shi, Hongtao Yao, Kang Zhang, Shuning Zheng, Zhenzhong Zhu, Jianbing Front Cardiovasc Med Cardiovascular Medicine Inflammation plays an important role in aortic dissection (AD). Macrophages are critically involved in the inflammation after aortic injury. Neuraminidases (NEUs) are a family of enzymes that catalyze the cleavage of terminal sialic acids from glycoproteins or glycolipids, which is emerging as a regulator of macrophage-associated immune responses. However, the role of neuraminidase 1 (NEU1) in pathological vascular remodeling of AD remains largely unknown. This study sought to characterize the role and identify the potential mechanism of NEU1 in pathological aortic degeneration. After β-aminopropionitrile monofumarate (BAPN) administration, NEU1 elevated significantly in the lesion zone of the aorta. Global or macrophage-specific NEU1 knockout (NEU1 CKO) mice had no baseline aortic defects but manifested improved aorta function, and decreased mortality due to aortic rupture. Improved outcomes in NEU1 CKO mice subjected to BAPN treatment were associated with the ameliorated vascular inflammation, lowered apoptosis, decreased reactive oxygen species production, mitigated extracellular matrix degradation, and improved M2 macrophage polarization. Furthermore, macrophages sorted from the aorta of NEU1 CKO mice displayed a significant increase of M2 macrophage markers and a marked decrease of M1 macrophage markers compared with the controls. To summarize, the present study demonstrated that macrophage-derived NEU1 is critical for vascular homeostasis. NEU1 exacerbates BAPN-induced pathological vascular remodeling. NEU1 may therefore represent a potential therapeutic target for the treatment of AD. Frontiers Media S.A. 2021-11-18 /pmc/articles/PMC8639188/ /pubmed/34869700 http://dx.doi.org/10.3389/fcvm.2021.788645 Text en Copyright © 2021 Wang, Chen, Peng, Zheng, Le, Guo, Ma, Shi, Yao, Zhang, Zheng and Zhu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cardiovascular Medicine Wang, Qian Chen, Zhaoyang Peng, Xiaoping Zheng, Zeqi Le, Aiping Guo, Junjie Ma, Leilei Shi, Hongtao Yao, Kang Zhang, Shuning Zheng, Zhenzhong Zhu, Jianbing Neuraminidase 1 Exacerbating Aortic Dissection by Governing a Pro-Inflammatory Program in Macrophages |
title | Neuraminidase 1 Exacerbating Aortic Dissection by Governing a Pro-Inflammatory Program in Macrophages |
title_full | Neuraminidase 1 Exacerbating Aortic Dissection by Governing a Pro-Inflammatory Program in Macrophages |
title_fullStr | Neuraminidase 1 Exacerbating Aortic Dissection by Governing a Pro-Inflammatory Program in Macrophages |
title_full_unstemmed | Neuraminidase 1 Exacerbating Aortic Dissection by Governing a Pro-Inflammatory Program in Macrophages |
title_short | Neuraminidase 1 Exacerbating Aortic Dissection by Governing a Pro-Inflammatory Program in Macrophages |
title_sort | neuraminidase 1 exacerbating aortic dissection by governing a pro-inflammatory program in macrophages |
topic | Cardiovascular Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8639188/ https://www.ncbi.nlm.nih.gov/pubmed/34869700 http://dx.doi.org/10.3389/fcvm.2021.788645 |
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