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MicroRNA‐199a‐5p aggravates angiotensin II–induced vascular smooth muscle cell senescence by targeting Sirtuin‐1 in abdominal aortic aneurysm

Vascular smooth muscle cells (VSMCs) senescence contributes to abdominal aortic aneurysm (AAA) formation although the underlying mechanisms remain unclear. This study aimed to investigate the role of miR‐199a‐5p in regulating VSMC senescence in AAA. VSMC senescence was determined by a senescence‐ass...

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Autores principales: Tao, Wuyuan, Hong, Yimei, He, Haiwei, Han, Qian, Mao, Mengmeng, Hu, Bei, Zhang, Hao, Huang, Xiaoran, You, Wei, Liang, Xiaoting, Zhang, Yuelin, Li, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366448/
https://www.ncbi.nlm.nih.gov/pubmed/34132029
http://dx.doi.org/10.1111/jcmm.16485
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author Tao, Wuyuan
Hong, Yimei
He, Haiwei
Han, Qian
Mao, Mengmeng
Hu, Bei
Zhang, Hao
Huang, Xiaoran
You, Wei
Liang, Xiaoting
Zhang, Yuelin
Li, Xin
author_facet Tao, Wuyuan
Hong, Yimei
He, Haiwei
Han, Qian
Mao, Mengmeng
Hu, Bei
Zhang, Hao
Huang, Xiaoran
You, Wei
Liang, Xiaoting
Zhang, Yuelin
Li, Xin
author_sort Tao, Wuyuan
collection PubMed
description Vascular smooth muscle cells (VSMCs) senescence contributes to abdominal aortic aneurysm (AAA) formation although the underlying mechanisms remain unclear. This study aimed to investigate the role of miR‐199a‐5p in regulating VSMC senescence in AAA. VSMC senescence was determined by a senescence‐associated β‐galactosidase (SA‐β‐gal) assay. RT‐PCR and Western blotting were performed to measure miRNA and protein level, respectively. The generation of reactive oxygen species (ROS) was evaluated by H2DCFDA staining. Dual‐luciferase reporter assay was used to validate the target gene of miR‐199a‐5p. VSMCs exhibited increased senescence in AAA tissue relative to healthy aortic tissue from control donors. Compared with VSMCs isolated from control donors (control‐VSMCs), those derived from patients with AAA (AAA‐VSMCs) exhibited increased cellular senescence and ROS production. Angiotensin II (Ang II) induced VSMC senescence by promoting ROS generation. The level of miR‐199a‐5p expression was upregulated in the plasma from AAA patients and Ang II–treated VSMCs. Mechanistically, Ang II treatment significantly elevated miR‐199a‐5p level, thereby stimulating ROS generation by repressing Sirt1 and consequent VSMC senescence. Nevertheless, Ang II–induced VSMC senescence was partially attenuated by a miR‐199a‐5p inhibitor or Sirt1 activator. Our study revealed that miR‐199a‐5p aggravates Ang II–induced VSMC senescence by targeting Sirt1 and that miR‐199a‐5p is a potential therapeutic target for AAA.
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spelling pubmed-83664482021-08-23 MicroRNA‐199a‐5p aggravates angiotensin II–induced vascular smooth muscle cell senescence by targeting Sirtuin‐1 in abdominal aortic aneurysm Tao, Wuyuan Hong, Yimei He, Haiwei Han, Qian Mao, Mengmeng Hu, Bei Zhang, Hao Huang, Xiaoran You, Wei Liang, Xiaoting Zhang, Yuelin Li, Xin J Cell Mol Med Original Articles Vascular smooth muscle cells (VSMCs) senescence contributes to abdominal aortic aneurysm (AAA) formation although the underlying mechanisms remain unclear. This study aimed to investigate the role of miR‐199a‐5p in regulating VSMC senescence in AAA. VSMC senescence was determined by a senescence‐associated β‐galactosidase (SA‐β‐gal) assay. RT‐PCR and Western blotting were performed to measure miRNA and protein level, respectively. The generation of reactive oxygen species (ROS) was evaluated by H2DCFDA staining. Dual‐luciferase reporter assay was used to validate the target gene of miR‐199a‐5p. VSMCs exhibited increased senescence in AAA tissue relative to healthy aortic tissue from control donors. Compared with VSMCs isolated from control donors (control‐VSMCs), those derived from patients with AAA (AAA‐VSMCs) exhibited increased cellular senescence and ROS production. Angiotensin II (Ang II) induced VSMC senescence by promoting ROS generation. The level of miR‐199a‐5p expression was upregulated in the plasma from AAA patients and Ang II–treated VSMCs. Mechanistically, Ang II treatment significantly elevated miR‐199a‐5p level, thereby stimulating ROS generation by repressing Sirt1 and consequent VSMC senescence. Nevertheless, Ang II–induced VSMC senescence was partially attenuated by a miR‐199a‐5p inhibitor or Sirt1 activator. Our study revealed that miR‐199a‐5p aggravates Ang II–induced VSMC senescence by targeting Sirt1 and that miR‐199a‐5p is a potential therapeutic target for AAA. John Wiley and Sons Inc. 2021-06-15 2021-07 /pmc/articles/PMC8366448/ /pubmed/34132029 http://dx.doi.org/10.1111/jcmm.16485 Text en © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Tao, Wuyuan
Hong, Yimei
He, Haiwei
Han, Qian
Mao, Mengmeng
Hu, Bei
Zhang, Hao
Huang, Xiaoran
You, Wei
Liang, Xiaoting
Zhang, Yuelin
Li, Xin
MicroRNA‐199a‐5p aggravates angiotensin II–induced vascular smooth muscle cell senescence by targeting Sirtuin‐1 in abdominal aortic aneurysm
title MicroRNA‐199a‐5p aggravates angiotensin II–induced vascular smooth muscle cell senescence by targeting Sirtuin‐1 in abdominal aortic aneurysm
title_full MicroRNA‐199a‐5p aggravates angiotensin II–induced vascular smooth muscle cell senescence by targeting Sirtuin‐1 in abdominal aortic aneurysm
title_fullStr MicroRNA‐199a‐5p aggravates angiotensin II–induced vascular smooth muscle cell senescence by targeting Sirtuin‐1 in abdominal aortic aneurysm
title_full_unstemmed MicroRNA‐199a‐5p aggravates angiotensin II–induced vascular smooth muscle cell senescence by targeting Sirtuin‐1 in abdominal aortic aneurysm
title_short MicroRNA‐199a‐5p aggravates angiotensin II–induced vascular smooth muscle cell senescence by targeting Sirtuin‐1 in abdominal aortic aneurysm
title_sort microrna‐199a‐5p aggravates angiotensin ii–induced vascular smooth muscle cell senescence by targeting sirtuin‐1 in abdominal aortic aneurysm
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366448/
https://www.ncbi.nlm.nih.gov/pubmed/34132029
http://dx.doi.org/10.1111/jcmm.16485
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