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Slow flow induces endothelial dysfunction by regulating thioredoxin-interacting protein-mediated oxidative metabolism and vascular inflammation

Endothelial cells are highly sensitive to hemodynamic shear stresses, which act in the blood flow’s direction on the blood vessel’s luminal surface. Thus, endothelial cells on that surface are exposed to various physiological and pathological stimuli, such as disturbed flow-induced shear stress, whi...

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Autores principales: Wang, Yongshun, Liu, Jingjin, Liu, Huadong, Sun, Xin, Chen, Ruimian, Liao, Bihong, Zeng, Xiaoyi, Zhang, Xiaoxin, Dong, Shaohong, Xia, Zhengyuan, Yuan, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9708747/
https://www.ncbi.nlm.nih.gov/pubmed/36465470
http://dx.doi.org/10.3389/fcvm.2022.1064375
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author Wang, Yongshun
Liu, Jingjin
Liu, Huadong
Sun, Xin
Chen, Ruimian
Liao, Bihong
Zeng, Xiaoyi
Zhang, Xiaoxin
Dong, Shaohong
Xia, Zhengyuan
Yuan, Jie
author_facet Wang, Yongshun
Liu, Jingjin
Liu, Huadong
Sun, Xin
Chen, Ruimian
Liao, Bihong
Zeng, Xiaoyi
Zhang, Xiaoxin
Dong, Shaohong
Xia, Zhengyuan
Yuan, Jie
author_sort Wang, Yongshun
collection PubMed
description Endothelial cells are highly sensitive to hemodynamic shear stresses, which act in the blood flow’s direction on the blood vessel’s luminal surface. Thus, endothelial cells on that surface are exposed to various physiological and pathological stimuli, such as disturbed flow-induced shear stress, which may exert effects on adaptive vascular diameter or structural wall remodeling. Here we showed that plasma thioredoxin-interactive protein (TXNIP) and malondialdehyde levels were significantly increased in patients with slow coronary flow. In addition, human endothelial cells exposed to disturbed flow exhibited increased levels of TXNIP in vitro. On the other hand, deletion of human endothelial TXNIP increased capillary formation, nitric oxide production and mitochondrial function, as well as lessened oxidative stress response and endothelial cell inflammation. Additional beneficial impacts from TXNIP deletion were also seen in a glucose utilization study, as reflected by augmented glucose uptake, lactate secretion and extracellular acidification rate. Taken together, our results suggested that TXNIP is a key component involved in mediating shear stress-induced inflammation, energy homeostasis, and glucose utilization, and that TXNIP may serve as a potentially novel endothelial dysfunction regulator.
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spelling pubmed-97087472022-12-01 Slow flow induces endothelial dysfunction by regulating thioredoxin-interacting protein-mediated oxidative metabolism and vascular inflammation Wang, Yongshun Liu, Jingjin Liu, Huadong Sun, Xin Chen, Ruimian Liao, Bihong Zeng, Xiaoyi Zhang, Xiaoxin Dong, Shaohong Xia, Zhengyuan Yuan, Jie Front Cardiovasc Med Cardiovascular Medicine Endothelial cells are highly sensitive to hemodynamic shear stresses, which act in the blood flow’s direction on the blood vessel’s luminal surface. Thus, endothelial cells on that surface are exposed to various physiological and pathological stimuli, such as disturbed flow-induced shear stress, which may exert effects on adaptive vascular diameter or structural wall remodeling. Here we showed that plasma thioredoxin-interactive protein (TXNIP) and malondialdehyde levels were significantly increased in patients with slow coronary flow. In addition, human endothelial cells exposed to disturbed flow exhibited increased levels of TXNIP in vitro. On the other hand, deletion of human endothelial TXNIP increased capillary formation, nitric oxide production and mitochondrial function, as well as lessened oxidative stress response and endothelial cell inflammation. Additional beneficial impacts from TXNIP deletion were also seen in a glucose utilization study, as reflected by augmented glucose uptake, lactate secretion and extracellular acidification rate. Taken together, our results suggested that TXNIP is a key component involved in mediating shear stress-induced inflammation, energy homeostasis, and glucose utilization, and that TXNIP may serve as a potentially novel endothelial dysfunction regulator. Frontiers Media S.A. 2022-11-16 /pmc/articles/PMC9708747/ /pubmed/36465470 http://dx.doi.org/10.3389/fcvm.2022.1064375 Text en Copyright © 2022 Wang, Liu, Liu, Sun, Chen, Liao, Zeng, Zhang, Dong, Xia and Yuan. 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 Cardiovascular Medicine
Wang, Yongshun
Liu, Jingjin
Liu, Huadong
Sun, Xin
Chen, Ruimian
Liao, Bihong
Zeng, Xiaoyi
Zhang, Xiaoxin
Dong, Shaohong
Xia, Zhengyuan
Yuan, Jie
Slow flow induces endothelial dysfunction by regulating thioredoxin-interacting protein-mediated oxidative metabolism and vascular inflammation
title Slow flow induces endothelial dysfunction by regulating thioredoxin-interacting protein-mediated oxidative metabolism and vascular inflammation
title_full Slow flow induces endothelial dysfunction by regulating thioredoxin-interacting protein-mediated oxidative metabolism and vascular inflammation
title_fullStr Slow flow induces endothelial dysfunction by regulating thioredoxin-interacting protein-mediated oxidative metabolism and vascular inflammation
title_full_unstemmed Slow flow induces endothelial dysfunction by regulating thioredoxin-interacting protein-mediated oxidative metabolism and vascular inflammation
title_short Slow flow induces endothelial dysfunction by regulating thioredoxin-interacting protein-mediated oxidative metabolism and vascular inflammation
title_sort slow flow induces endothelial dysfunction by regulating thioredoxin-interacting protein-mediated oxidative metabolism and vascular inflammation
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9708747/
https://www.ncbi.nlm.nih.gov/pubmed/36465470
http://dx.doi.org/10.3389/fcvm.2022.1064375
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