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Oscillatory shear stress-induced downregulation of TET1s injures vascular endothelial planar cell polarity by suppression of actin polymerization

Vascular endothelial polarity induced by blood flow plays crucial roles in the development of atherosclerosis. Loss of endothelial polarity leads to an increase in permeability and leukocyte recruitment, which are crucial hallmarks of atherosclerotic initiation. Endothelial cells exhibit a morpholog...

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Autores principales: Qu, Kai, Wang, Caihong, Huang, Lu, Qin, Xian, Zhang, Kun, Qiu, Juhui, Wang, Guixue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AIP Publishing LLC 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10393427/
https://www.ncbi.nlm.nih.gov/pubmed/37533755
http://dx.doi.org/10.1063/5.0141289
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author Qu, Kai
Wang, Caihong
Huang, Lu
Qin, Xian
Zhang, Kun
Qiu, Juhui
Wang, Guixue
author_facet Qu, Kai
Wang, Caihong
Huang, Lu
Qin, Xian
Zhang, Kun
Qiu, Juhui
Wang, Guixue
author_sort Qu, Kai
collection PubMed
description Vascular endothelial polarity induced by blood flow plays crucial roles in the development of atherosclerosis. Loss of endothelial polarity leads to an increase in permeability and leukocyte recruitment, which are crucial hallmarks of atherosclerotic initiation. Endothelial cells exhibit a morphological adaptation to hemodynamic shear stress and possesses planar cell polarity to the direction of blood flow. However, the mechanism of how hemodynamic shear stress regulates endothelial planar cell polarity has not been firmly established. Here, we found that TET1s, a short isoform of Tet methylcytosine dioxygenase 1, was a mediator in the regulation of the planar cell polarity in endothelial cells in response to hemodynamic shear stress. In the process, low expression of TET1s induced by oscillatory shear stress led to the endothelial planar polarity damage through inhibition of F-actin polymerization. TET1s can regulate demethylation level of the sFRP-1 promoter to alter the expression of sFRP-1, which affects the interaction of sFRP-1/Fzd4 and F-actin polymerization. Our study revealed the mechanism of how TET1s mediates endothelial planar cell polarity in response to hemodynamic shear stress and provides a new insight for the prevention of atherosclerosis.
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spelling pubmed-103934272023-08-02 Oscillatory shear stress-induced downregulation of TET1s injures vascular endothelial planar cell polarity by suppression of actin polymerization Qu, Kai Wang, Caihong Huang, Lu Qin, Xian Zhang, Kun Qiu, Juhui Wang, Guixue APL Bioeng Articles Vascular endothelial polarity induced by blood flow plays crucial roles in the development of atherosclerosis. Loss of endothelial polarity leads to an increase in permeability and leukocyte recruitment, which are crucial hallmarks of atherosclerotic initiation. Endothelial cells exhibit a morphological adaptation to hemodynamic shear stress and possesses planar cell polarity to the direction of blood flow. However, the mechanism of how hemodynamic shear stress regulates endothelial planar cell polarity has not been firmly established. Here, we found that TET1s, a short isoform of Tet methylcytosine dioxygenase 1, was a mediator in the regulation of the planar cell polarity in endothelial cells in response to hemodynamic shear stress. In the process, low expression of TET1s induced by oscillatory shear stress led to the endothelial planar polarity damage through inhibition of F-actin polymerization. TET1s can regulate demethylation level of the sFRP-1 promoter to alter the expression of sFRP-1, which affects the interaction of sFRP-1/Fzd4 and F-actin polymerization. Our study revealed the mechanism of how TET1s mediates endothelial planar cell polarity in response to hemodynamic shear stress and provides a new insight for the prevention of atherosclerosis. AIP Publishing LLC 2023-07-31 /pmc/articles/PMC10393427/ /pubmed/37533755 http://dx.doi.org/10.1063/5.0141289 Text en © 2023 Author(s). https://creativecommons.org/licenses/by/4.0/All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Articles
Qu, Kai
Wang, Caihong
Huang, Lu
Qin, Xian
Zhang, Kun
Qiu, Juhui
Wang, Guixue
Oscillatory shear stress-induced downregulation of TET1s injures vascular endothelial planar cell polarity by suppression of actin polymerization
title Oscillatory shear stress-induced downregulation of TET1s injures vascular endothelial planar cell polarity by suppression of actin polymerization
title_full Oscillatory shear stress-induced downregulation of TET1s injures vascular endothelial planar cell polarity by suppression of actin polymerization
title_fullStr Oscillatory shear stress-induced downregulation of TET1s injures vascular endothelial planar cell polarity by suppression of actin polymerization
title_full_unstemmed Oscillatory shear stress-induced downregulation of TET1s injures vascular endothelial planar cell polarity by suppression of actin polymerization
title_short Oscillatory shear stress-induced downregulation of TET1s injures vascular endothelial planar cell polarity by suppression of actin polymerization
title_sort oscillatory shear stress-induced downregulation of tet1s injures vascular endothelial planar cell polarity by suppression of actin polymerization
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10393427/
https://www.ncbi.nlm.nih.gov/pubmed/37533755
http://dx.doi.org/10.1063/5.0141289
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