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AT1R Regulates Macrophage Polarization Through YAP and Regulates Aortic Dissection Incidence

Aortic dissection (AD) is one of the most fatal cardiovascular emergency. At the anatomical level, AD occurs due to the formation of intimal tears. However, the molecular mechanism underlying this phenomenon remains unknown. Angiotensin II (Ang II) is a important effector in the development of cardi...

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Autores principales: Wang, Xinhao, Zhang, Hongpeng, Ge, Yangyang, Cao, Long, He, Yuan, Sun, Guoyi, Jia, Senhao, Ma, Airong, Liu, Jie, Rong, Dan, Guo, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299470/
https://www.ncbi.nlm.nih.gov/pubmed/34305627
http://dx.doi.org/10.3389/fphys.2021.644903
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author Wang, Xinhao
Zhang, Hongpeng
Ge, Yangyang
Cao, Long
He, Yuan
Sun, Guoyi
Jia, Senhao
Ma, Airong
Liu, Jie
Rong, Dan
Guo, Wei
author_facet Wang, Xinhao
Zhang, Hongpeng
Ge, Yangyang
Cao, Long
He, Yuan
Sun, Guoyi
Jia, Senhao
Ma, Airong
Liu, Jie
Rong, Dan
Guo, Wei
author_sort Wang, Xinhao
collection PubMed
description Aortic dissection (AD) is one of the most fatal cardiovascular emergency. At the anatomical level, AD occurs due to the formation of intimal tears. However, the molecular mechanism underlying this phenomenon remains unknown. Angiotensin II (Ang II) is a important effector in the development of cardiovascular disease that acts through binding to angiotensin type 1 receptor (AT1R). Yes-associated protein (YAP) was recently recognized as a key protein in macrophage activation. To determine whether AT1R and YAP are involved in macrophage-induced endothelial cell (EC) inflammation and AD incidence, we co-cultured THP-1 cells and HAECs in transwell chambers under different culture conditions and apply different conditions to the AD mice model. The results showed that Ang II promoted macrophage M1 polarization and adhesion, upregulated YAP phosphorylation, and induced EC injury that was related to increased levels of multiple pro-inflammatory chemokines. Blocking AT1R function pharmacologically or by transfection with AT1R siRNA can reduce the pro-inflammatory effect induced by Ang II. In addition, siRNA knock down of YAP expression further aggravated the pro-inflammatory effects of Ang II. Treatment with ARB effectively alleviated these pro-inflammatory effects. In the mice AD model, ARB effectively reduced the incidence of AD in mice, decreased M1 macrophages infiltration and AT1R content in the aortic wall and increased the tissue content of YAP. We found that AT1R induces YAP phosphorylation through binding to Ang II, and further promotes macrophage M1 polarization and adhesion to ECs. ARB reduces the incidence of AD in mice and affect macrophage polarization in mice aorta.
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spelling pubmed-82994702021-07-24 AT1R Regulates Macrophage Polarization Through YAP and Regulates Aortic Dissection Incidence Wang, Xinhao Zhang, Hongpeng Ge, Yangyang Cao, Long He, Yuan Sun, Guoyi Jia, Senhao Ma, Airong Liu, Jie Rong, Dan Guo, Wei Front Physiol Physiology Aortic dissection (AD) is one of the most fatal cardiovascular emergency. At the anatomical level, AD occurs due to the formation of intimal tears. However, the molecular mechanism underlying this phenomenon remains unknown. Angiotensin II (Ang II) is a important effector in the development of cardiovascular disease that acts through binding to angiotensin type 1 receptor (AT1R). Yes-associated protein (YAP) was recently recognized as a key protein in macrophage activation. To determine whether AT1R and YAP are involved in macrophage-induced endothelial cell (EC) inflammation and AD incidence, we co-cultured THP-1 cells and HAECs in transwell chambers under different culture conditions and apply different conditions to the AD mice model. The results showed that Ang II promoted macrophage M1 polarization and adhesion, upregulated YAP phosphorylation, and induced EC injury that was related to increased levels of multiple pro-inflammatory chemokines. Blocking AT1R function pharmacologically or by transfection with AT1R siRNA can reduce the pro-inflammatory effect induced by Ang II. In addition, siRNA knock down of YAP expression further aggravated the pro-inflammatory effects of Ang II. Treatment with ARB effectively alleviated these pro-inflammatory effects. In the mice AD model, ARB effectively reduced the incidence of AD in mice, decreased M1 macrophages infiltration and AT1R content in the aortic wall and increased the tissue content of YAP. We found that AT1R induces YAP phosphorylation through binding to Ang II, and further promotes macrophage M1 polarization and adhesion to ECs. ARB reduces the incidence of AD in mice and affect macrophage polarization in mice aorta. Frontiers Media S.A. 2021-07-09 /pmc/articles/PMC8299470/ /pubmed/34305627 http://dx.doi.org/10.3389/fphys.2021.644903 Text en Copyright © 2021 Wang, Zhang, Ge, Cao, He, Sun, Jia, Ma, Liu, Rong and Guo. 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 Physiology
Wang, Xinhao
Zhang, Hongpeng
Ge, Yangyang
Cao, Long
He, Yuan
Sun, Guoyi
Jia, Senhao
Ma, Airong
Liu, Jie
Rong, Dan
Guo, Wei
AT1R Regulates Macrophage Polarization Through YAP and Regulates Aortic Dissection Incidence
title AT1R Regulates Macrophage Polarization Through YAP and Regulates Aortic Dissection Incidence
title_full AT1R Regulates Macrophage Polarization Through YAP and Regulates Aortic Dissection Incidence
title_fullStr AT1R Regulates Macrophage Polarization Through YAP and Regulates Aortic Dissection Incidence
title_full_unstemmed AT1R Regulates Macrophage Polarization Through YAP and Regulates Aortic Dissection Incidence
title_short AT1R Regulates Macrophage Polarization Through YAP and Regulates Aortic Dissection Incidence
title_sort at1r regulates macrophage polarization through yap and regulates aortic dissection incidence
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299470/
https://www.ncbi.nlm.nih.gov/pubmed/34305627
http://dx.doi.org/10.3389/fphys.2021.644903
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