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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...

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Autores principales: 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.
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
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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.
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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
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