Cargando…
Intermittent Hypoxia-Induced Activation of Endothelial Cells Is Mediated via Sympathetic Activation-Dependent Catecholamine Release
Obstructive sleep apnea (OSA) is a common breathing disorder affecting a significant percentage of the adult population. OSA is an independent risk factor for cardiovascular disease (CVD); however, the underlying mechanisms are not completely understood. Since the severity of hypoxia correlates with...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311436/ https://www.ncbi.nlm.nih.gov/pubmed/34322038 http://dx.doi.org/10.3389/fphys.2021.701995 |
_version_ | 1783728954809516032 |
---|---|
author | Cetin-Atalay, Rengul Meliton, Angelo Y. Wu, David Woods, Parker S. Sun, Kaitlyn A. Peng, Ying-Jie Nanduri, Jayasri Su, Xiaoyu Fang, Yun Hamanaka, Robert B. Prabhakar, Nanduri Mutlu, Gökhan M. |
author_facet | Cetin-Atalay, Rengul Meliton, Angelo Y. Wu, David Woods, Parker S. Sun, Kaitlyn A. Peng, Ying-Jie Nanduri, Jayasri Su, Xiaoyu Fang, Yun Hamanaka, Robert B. Prabhakar, Nanduri Mutlu, Gökhan M. |
author_sort | Cetin-Atalay, Rengul |
collection | PubMed |
description | Obstructive sleep apnea (OSA) is a common breathing disorder affecting a significant percentage of the adult population. OSA is an independent risk factor for cardiovascular disease (CVD); however, the underlying mechanisms are not completely understood. Since the severity of hypoxia correlates with some of the cardiovascular effects, intermittent hypoxia (IH) is thought to be one of the mechanisms by which OSA may cause CVD. Here, we investigated the effect of IH on endothelial cell (EC) activation, characterized by the expression of inflammatory genes, that is known to play an important role in the pathogenesis of CVD. Exposure of C57BL/6 mice to IH led to aortic EC activation, while in vitro exposure of ECs to IH failed to do so, suggesting that IH does not induce EC activation directly, but indirectly. One of the consequences of IH is activation of the sympathetic nervous system and catecholamine release. We found that exposure of mice to IH caused elevation of circulating levels of catecholamines. Inhibition of the IH-induced increase in catecholamines by pharmacologic inhibition or by adrenalectomy or carotid body ablation prevented the IH-induced EC activation in mice. Supporting a key role for catecholamines, epinephrine alone was sufficient to cause EC activation in vivo and in vitro. Together, these results suggested that IH does not directly induce EC activation, but does so indirectly via release of catecholamines. These results suggest that targeting IH-induced sympathetic nerve activity and catecholamine release may be a potential therapeutic target to attenuate the CV effects of OSA. |
format | Online Article Text |
id | pubmed-8311436 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83114362021-07-27 Intermittent Hypoxia-Induced Activation of Endothelial Cells Is Mediated via Sympathetic Activation-Dependent Catecholamine Release Cetin-Atalay, Rengul Meliton, Angelo Y. Wu, David Woods, Parker S. Sun, Kaitlyn A. Peng, Ying-Jie Nanduri, Jayasri Su, Xiaoyu Fang, Yun Hamanaka, Robert B. Prabhakar, Nanduri Mutlu, Gökhan M. Front Physiol Physiology Obstructive sleep apnea (OSA) is a common breathing disorder affecting a significant percentage of the adult population. OSA is an independent risk factor for cardiovascular disease (CVD); however, the underlying mechanisms are not completely understood. Since the severity of hypoxia correlates with some of the cardiovascular effects, intermittent hypoxia (IH) is thought to be one of the mechanisms by which OSA may cause CVD. Here, we investigated the effect of IH on endothelial cell (EC) activation, characterized by the expression of inflammatory genes, that is known to play an important role in the pathogenesis of CVD. Exposure of C57BL/6 mice to IH led to aortic EC activation, while in vitro exposure of ECs to IH failed to do so, suggesting that IH does not induce EC activation directly, but indirectly. One of the consequences of IH is activation of the sympathetic nervous system and catecholamine release. We found that exposure of mice to IH caused elevation of circulating levels of catecholamines. Inhibition of the IH-induced increase in catecholamines by pharmacologic inhibition or by adrenalectomy or carotid body ablation prevented the IH-induced EC activation in mice. Supporting a key role for catecholamines, epinephrine alone was sufficient to cause EC activation in vivo and in vitro. Together, these results suggested that IH does not directly induce EC activation, but does so indirectly via release of catecholamines. These results suggest that targeting IH-induced sympathetic nerve activity and catecholamine release may be a potential therapeutic target to attenuate the CV effects of OSA. Frontiers Media S.A. 2021-07-12 /pmc/articles/PMC8311436/ /pubmed/34322038 http://dx.doi.org/10.3389/fphys.2021.701995 Text en Copyright © 2021 Cetin-Atalay, Meliton, Wu, Woods, Sun, Peng, Nanduri, Su, Fang, Hamanaka, Prabhakar and Mutlu. 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 Cetin-Atalay, Rengul Meliton, Angelo Y. Wu, David Woods, Parker S. Sun, Kaitlyn A. Peng, Ying-Jie Nanduri, Jayasri Su, Xiaoyu Fang, Yun Hamanaka, Robert B. Prabhakar, Nanduri Mutlu, Gökhan M. Intermittent Hypoxia-Induced Activation of Endothelial Cells Is Mediated via Sympathetic Activation-Dependent Catecholamine Release |
title | Intermittent Hypoxia-Induced Activation of Endothelial Cells Is Mediated via Sympathetic Activation-Dependent Catecholamine Release |
title_full | Intermittent Hypoxia-Induced Activation of Endothelial Cells Is Mediated via Sympathetic Activation-Dependent Catecholamine Release |
title_fullStr | Intermittent Hypoxia-Induced Activation of Endothelial Cells Is Mediated via Sympathetic Activation-Dependent Catecholamine Release |
title_full_unstemmed | Intermittent Hypoxia-Induced Activation of Endothelial Cells Is Mediated via Sympathetic Activation-Dependent Catecholamine Release |
title_short | Intermittent Hypoxia-Induced Activation of Endothelial Cells Is Mediated via Sympathetic Activation-Dependent Catecholamine Release |
title_sort | intermittent hypoxia-induced activation of endothelial cells is mediated via sympathetic activation-dependent catecholamine release |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311436/ https://www.ncbi.nlm.nih.gov/pubmed/34322038 http://dx.doi.org/10.3389/fphys.2021.701995 |
work_keys_str_mv | AT cetinatalayrengul intermittenthypoxiainducedactivationofendothelialcellsismediatedviasympatheticactivationdependentcatecholaminerelease AT melitonangeloy intermittenthypoxiainducedactivationofendothelialcellsismediatedviasympatheticactivationdependentcatecholaminerelease AT wudavid intermittenthypoxiainducedactivationofendothelialcellsismediatedviasympatheticactivationdependentcatecholaminerelease AT woodsparkers intermittenthypoxiainducedactivationofendothelialcellsismediatedviasympatheticactivationdependentcatecholaminerelease AT sunkaitlyna intermittenthypoxiainducedactivationofendothelialcellsismediatedviasympatheticactivationdependentcatecholaminerelease AT pengyingjie intermittenthypoxiainducedactivationofendothelialcellsismediatedviasympatheticactivationdependentcatecholaminerelease AT nandurijayasri intermittenthypoxiainducedactivationofendothelialcellsismediatedviasympatheticactivationdependentcatecholaminerelease AT suxiaoyu intermittenthypoxiainducedactivationofendothelialcellsismediatedviasympatheticactivationdependentcatecholaminerelease AT fangyun intermittenthypoxiainducedactivationofendothelialcellsismediatedviasympatheticactivationdependentcatecholaminerelease AT hamanakarobertb intermittenthypoxiainducedactivationofendothelialcellsismediatedviasympatheticactivationdependentcatecholaminerelease AT prabhakarnanduri intermittenthypoxiainducedactivationofendothelialcellsismediatedviasympatheticactivationdependentcatecholaminerelease AT mutlugokhanm intermittenthypoxiainducedactivationofendothelialcellsismediatedviasympatheticactivationdependentcatecholaminerelease |