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Chronic Intermittent Hypoxia Regulates CaMKII-Dependent MAPK Signaling to Promote the Initiation of Abdominal Aortic Aneurysm
Obstructive sleep apnea (OSA) is highly prevalent in patients with abdominal aortic aneurysm (AAA). However, the effects of OSA on AAA initiation in a murine model of sleep apnea have not been completely studied. In this paper, Apoe(−/−) C57BL/6 mice infused with angiotensin II (Ang II) were placed...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8714336/ https://www.ncbi.nlm.nih.gov/pubmed/34970414 http://dx.doi.org/10.1155/2021/2502324 |
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author | Xu, Chenyu Xu, Jun Zou, Chunfang Li, Qian Mao, Shan Shi, Ying Tan, Yan Gu, Wei Ye, Liang |
author_facet | Xu, Chenyu Xu, Jun Zou, Chunfang Li, Qian Mao, Shan Shi, Ying Tan, Yan Gu, Wei Ye, Liang |
author_sort | Xu, Chenyu |
collection | PubMed |
description | Obstructive sleep apnea (OSA) is highly prevalent in patients with abdominal aortic aneurysm (AAA). However, the effects of OSA on AAA initiation in a murine model of sleep apnea have not been completely studied. In this paper, Apoe(−/−) C57BL/6 mice infused with angiotensin II (Ang II) were placed in chronic intermittent hypoxia (CIH) condition for inducing OSA-related AAA. CIH significantly promoted the incidence of AAA and inhibited the survival of mice. By performing ultrasonography and elastic Van Gieson staining, CIH was found to be effective in promoting aortic dilation and elastin degradation. Immunohistochemical and zymography results show that CIH upregulated the expression and activity of MMP2 and MMP9 and upregulated MCP1 expression while downregulating α-SMA expression. Also, CIH exposure promoted ROS generation, apoptosis, and mitochondria damage in vascular smooth muscle cells (VSMCs), which were measured by ROS assay, TUNEL staining, and transmission electron microscopy. The result of RNA sequencing of mouse aortas displayed that 232 mRNAs were differently expressed between Ang II and Ang II+CIH groups, and CaMKII-dependent p38/Jnk was confirmed as one downstream signaling of CIH. CaMKII-IN-1, an inhibitor of CaMKII, eliminated the effects of CIH on the loss of primary VSMCs. To conclude, a mouse model of OSA-related AAA, which contains the phenotypes of both AAA and OSA, was established in this study. We suggested CIH as a risk factor of AAA initiation through CaMKII-dependent MAPK signaling. |
format | Online Article Text |
id | pubmed-8714336 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-87143362021-12-29 Chronic Intermittent Hypoxia Regulates CaMKII-Dependent MAPK Signaling to Promote the Initiation of Abdominal Aortic Aneurysm Xu, Chenyu Xu, Jun Zou, Chunfang Li, Qian Mao, Shan Shi, Ying Tan, Yan Gu, Wei Ye, Liang Oxid Med Cell Longev Research Article Obstructive sleep apnea (OSA) is highly prevalent in patients with abdominal aortic aneurysm (AAA). However, the effects of OSA on AAA initiation in a murine model of sleep apnea have not been completely studied. In this paper, Apoe(−/−) C57BL/6 mice infused with angiotensin II (Ang II) were placed in chronic intermittent hypoxia (CIH) condition for inducing OSA-related AAA. CIH significantly promoted the incidence of AAA and inhibited the survival of mice. By performing ultrasonography and elastic Van Gieson staining, CIH was found to be effective in promoting aortic dilation and elastin degradation. Immunohistochemical and zymography results show that CIH upregulated the expression and activity of MMP2 and MMP9 and upregulated MCP1 expression while downregulating α-SMA expression. Also, CIH exposure promoted ROS generation, apoptosis, and mitochondria damage in vascular smooth muscle cells (VSMCs), which were measured by ROS assay, TUNEL staining, and transmission electron microscopy. The result of RNA sequencing of mouse aortas displayed that 232 mRNAs were differently expressed between Ang II and Ang II+CIH groups, and CaMKII-dependent p38/Jnk was confirmed as one downstream signaling of CIH. CaMKII-IN-1, an inhibitor of CaMKII, eliminated the effects of CIH on the loss of primary VSMCs. To conclude, a mouse model of OSA-related AAA, which contains the phenotypes of both AAA and OSA, was established in this study. We suggested CIH as a risk factor of AAA initiation through CaMKII-dependent MAPK signaling. Hindawi 2021-12-21 /pmc/articles/PMC8714336/ /pubmed/34970414 http://dx.doi.org/10.1155/2021/2502324 Text en Copyright © 2021 Chenyu Xu et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Xu, Chenyu Xu, Jun Zou, Chunfang Li, Qian Mao, Shan Shi, Ying Tan, Yan Gu, Wei Ye, Liang Chronic Intermittent Hypoxia Regulates CaMKII-Dependent MAPK Signaling to Promote the Initiation of Abdominal Aortic Aneurysm |
title | Chronic Intermittent Hypoxia Regulates CaMKII-Dependent MAPK Signaling to Promote the Initiation of Abdominal Aortic Aneurysm |
title_full | Chronic Intermittent Hypoxia Regulates CaMKII-Dependent MAPK Signaling to Promote the Initiation of Abdominal Aortic Aneurysm |
title_fullStr | Chronic Intermittent Hypoxia Regulates CaMKII-Dependent MAPK Signaling to Promote the Initiation of Abdominal Aortic Aneurysm |
title_full_unstemmed | Chronic Intermittent Hypoxia Regulates CaMKII-Dependent MAPK Signaling to Promote the Initiation of Abdominal Aortic Aneurysm |
title_short | Chronic Intermittent Hypoxia Regulates CaMKII-Dependent MAPK Signaling to Promote the Initiation of Abdominal Aortic Aneurysm |
title_sort | chronic intermittent hypoxia regulates camkii-dependent mapk signaling to promote the initiation of abdominal aortic aneurysm |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8714336/ https://www.ncbi.nlm.nih.gov/pubmed/34970414 http://dx.doi.org/10.1155/2021/2502324 |
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