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...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:641b8f5780734be7b6ba049bbfa163662021-11-18T07:38:13ZNeuraminidase 1 Exacerbating Aortic Dissection by Governing a Pro-Inflammatory Program in Macrophages2297-055X10.3389/fcvm.2021.788645https://doaj.org/article/641b8f5780734be7b6ba049bbfa163662021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcvm.2021.788645/fullhttps://doaj.org/toc/2297-055XInflammation 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.Qian WangZhaoyang ChenXiaoping PengXiaoping PengZeqi ZhengZeqi ZhengAiping LeJunjie GuoLeilei MaHongtao ShiKang YaoShuning ZhangZhenzhong ZhengZhenzhong ZhengJianbing ZhuJianbing ZhuFrontiers Media S.A.articleNEU1aortic dissectionvascular remodelingmacrophage polarizationMMPDiseases of the circulatory (Cardiovascular) systemRC666-701ENFrontiers in Cardiovascular Medicine, Vol 8 (2021) |
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DOAJ |
| language |
EN |
| topic |
NEU1 aortic dissection vascular remodeling macrophage polarization MMP Diseases of the circulatory (Cardiovascular) system RC666-701 |
| spellingShingle |
NEU1 aortic dissection vascular remodeling macrophage polarization MMP Diseases of the circulatory (Cardiovascular) system RC666-701 Qian Wang Zhaoyang Chen Xiaoping Peng Xiaoping Peng Zeqi Zheng Zeqi Zheng Aiping Le Junjie Guo Leilei Ma Hongtao Shi Kang Yao Shuning Zhang Zhenzhong Zheng Zhenzhong Zheng Jianbing Zhu Jianbing Zhu Neuraminidase 1 Exacerbating Aortic Dissection by Governing a Pro-Inflammatory Program in Macrophages |
| 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 |
article |
| author |
Qian Wang Zhaoyang Chen Xiaoping Peng Xiaoping Peng Zeqi Zheng Zeqi Zheng Aiping Le Junjie Guo Leilei Ma Hongtao Shi Kang Yao Shuning Zhang Zhenzhong Zheng Zhenzhong Zheng Jianbing Zhu Jianbing Zhu |
| author_facet |
Qian Wang Zhaoyang Chen Xiaoping Peng Xiaoping Peng Zeqi Zheng Zeqi Zheng Aiping Le Junjie Guo Leilei Ma Hongtao Shi Kang Yao Shuning Zhang Zhenzhong Zheng Zhenzhong Zheng Jianbing Zhu Jianbing Zhu |
| author_sort |
Qian Wang |
| title |
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_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_sort |
neuraminidase 1 exacerbating aortic dissection by governing a pro-inflammatory program in macrophages |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/641b8f5780734be7b6ba049bbfa16366 |
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