Intermittent Hypoxia Activates Duration-Dependent Protective and Injurious Mechanisms in Mouse Lung Endothelial Cells
Intermittent hypoxia is a major factor in clinical conditions like the obstructive sleep apnea syndrome or the cyclic recruitment and derecruitment of atelectasis in acute respiratory distress syndrome and positive pressure mechanical ventilation. In vivo investigations of the direct impact of inter...
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doaj-4d0ef20898844efdb089f4cdb52dc3882020-11-24T21:02:15ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2018-12-01910.3389/fphys.2018.01754407605Intermittent Hypoxia Activates Duration-Dependent Protective and Injurious Mechanisms in Mouse Lung Endothelial CellsPeter Wohlrab0Lourdes Soto-Gonzales1Thomas Benesch2Max Paul Winter3Irene Marthe Lang4Klaus Markstaller5Verena Tretter6Klaus Ulrich Klein7Department of Anaesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Vienna, AustriaDepartment of Anaesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Vienna, AustriaInstitute for International Development, University of Vienna, Vienna, AustriaDepartment of Internal Medicine II, Medical University of Vienna, Vienna, AustriaDepartment of Internal Medicine II, Medical University of Vienna, Vienna, AustriaDepartment of Anaesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Vienna, AustriaDepartment of Anaesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Vienna, AustriaDepartment of Anaesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Vienna, AustriaIntermittent hypoxia is a major factor in clinical conditions like the obstructive sleep apnea syndrome or the cyclic recruitment and derecruitment of atelectasis in acute respiratory distress syndrome and positive pressure mechanical ventilation. In vivo investigations of the direct impact of intermittent hypoxia are frequently hampered by multiple co-morbidities of patients. Therefore, cell culture experiments are important model systems to elucidate molecular mechanisms that are involved in the cellular response to alternating oxygen conditions and could represent future targets for tailored therapies. In this study, we focused on mouse lung endothelial cells as a first frontier to encounter altered oxygen due to disturbances in airway or lung function, that play an important role in the development of secondary diseases like vascular disease and pulmonary hypertension. We analyzed key markers for endothelial function including cell adhesion molecules, molecules involved in regulation of fibrinolysis, hemostasis, redox balance, and regulators of gene expression like miRNAs. Results show that short-time exposure to intermittent hypoxia has little impact on vitality and health of cells. At early timepoints and up to 24 h, many endothelial markers are unchanged in their expression and some indicators of injury are even downregulated. However, in the long-term, multiple signaling pathways are activated, that ultimately result in cellular inflammation, oxidative stress, and apoptosis.https://www.frontiersin.org/article/10.3389/fphys.2018.01754/fulllung endotheliumintermittent hypoxiaobstructive sleep apneaalternating oxygen conditionsatelectasis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Peter Wohlrab Lourdes Soto-Gonzales Thomas Benesch Max Paul Winter Irene Marthe Lang Klaus Markstaller Verena Tretter Klaus Ulrich Klein |
spellingShingle |
Peter Wohlrab Lourdes Soto-Gonzales Thomas Benesch Max Paul Winter Irene Marthe Lang Klaus Markstaller Verena Tretter Klaus Ulrich Klein Intermittent Hypoxia Activates Duration-Dependent Protective and Injurious Mechanisms in Mouse Lung Endothelial Cells Frontiers in Physiology lung endothelium intermittent hypoxia obstructive sleep apnea alternating oxygen conditions atelectasis |
author_facet |
Peter Wohlrab Lourdes Soto-Gonzales Thomas Benesch Max Paul Winter Irene Marthe Lang Klaus Markstaller Verena Tretter Klaus Ulrich Klein |
author_sort |
Peter Wohlrab |
title |
Intermittent Hypoxia Activates Duration-Dependent Protective and Injurious Mechanisms in Mouse Lung Endothelial Cells |
title_short |
Intermittent Hypoxia Activates Duration-Dependent Protective and Injurious Mechanisms in Mouse Lung Endothelial Cells |
title_full |
Intermittent Hypoxia Activates Duration-Dependent Protective and Injurious Mechanisms in Mouse Lung Endothelial Cells |
title_fullStr |
Intermittent Hypoxia Activates Duration-Dependent Protective and Injurious Mechanisms in Mouse Lung Endothelial Cells |
title_full_unstemmed |
Intermittent Hypoxia Activates Duration-Dependent Protective and Injurious Mechanisms in Mouse Lung Endothelial Cells |
title_sort |
intermittent hypoxia activates duration-dependent protective and injurious mechanisms in mouse lung endothelial cells |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Physiology |
issn |
1664-042X |
publishDate |
2018-12-01 |
description |
Intermittent hypoxia is a major factor in clinical conditions like the obstructive sleep apnea syndrome or the cyclic recruitment and derecruitment of atelectasis in acute respiratory distress syndrome and positive pressure mechanical ventilation. In vivo investigations of the direct impact of intermittent hypoxia are frequently hampered by multiple co-morbidities of patients. Therefore, cell culture experiments are important model systems to elucidate molecular mechanisms that are involved in the cellular response to alternating oxygen conditions and could represent future targets for tailored therapies. In this study, we focused on mouse lung endothelial cells as a first frontier to encounter altered oxygen due to disturbances in airway or lung function, that play an important role in the development of secondary diseases like vascular disease and pulmonary hypertension. We analyzed key markers for endothelial function including cell adhesion molecules, molecules involved in regulation of fibrinolysis, hemostasis, redox balance, and regulators of gene expression like miRNAs. Results show that short-time exposure to intermittent hypoxia has little impact on vitality and health of cells. At early timepoints and up to 24 h, many endothelial markers are unchanged in their expression and some indicators of injury are even downregulated. However, in the long-term, multiple signaling pathways are activated, that ultimately result in cellular inflammation, oxidative stress, and apoptosis. |
topic |
lung endothelium intermittent hypoxia obstructive sleep apnea alternating oxygen conditions atelectasis |
url |
https://www.frontiersin.org/article/10.3389/fphys.2018.01754/full |
work_keys_str_mv |
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1716776060925771776 |