The Proteome of Extracellular Vesicles Released from Pulmonary Microvascular Endothelium Reveals Impact of Oxygen Conditions on Biotrauma

The lung can experience different oxygen concentrations, low as in hypoxia, high as under supplemental oxygen therapy, or oscillating during intermittent hypoxia as in obstructive sleep apnea or intermittent hypoxia/hyperoxia due to cyclic atelectasis in the ventilated patient. This study aimed to c...

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Main Authors: Wolfgang Schaubmayr, Beatrix Hochreiter, Eva Hunyadi-Gulyas, Louise Riegler, Katy Schmidt, Akos Tiboldi, Bernhard Moser, Klaus U. Klein, Katharina Krenn, Gisela Scharbert, Thomas Mohr, Johannes A. Schmid, Andreas Spittler, Verena Tretter
Format: Article
Language:English
Published: MDPI AG 2024-02-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/25/4/2415
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author Wolfgang Schaubmayr
Beatrix Hochreiter
Eva Hunyadi-Gulyas
Louise Riegler
Katy Schmidt
Akos Tiboldi
Bernhard Moser
Klaus U. Klein
Katharina Krenn
Gisela Scharbert
Thomas Mohr
Johannes A. Schmid
Andreas Spittler
Verena Tretter
author_facet Wolfgang Schaubmayr
Beatrix Hochreiter
Eva Hunyadi-Gulyas
Louise Riegler
Katy Schmidt
Akos Tiboldi
Bernhard Moser
Klaus U. Klein
Katharina Krenn
Gisela Scharbert
Thomas Mohr
Johannes A. Schmid
Andreas Spittler
Verena Tretter
author_sort Wolfgang Schaubmayr
collection DOAJ
description The lung can experience different oxygen concentrations, low as in hypoxia, high as under supplemental oxygen therapy, or oscillating during intermittent hypoxia as in obstructive sleep apnea or intermittent hypoxia/hyperoxia due to cyclic atelectasis in the ventilated patient. This study aimed to characterize the oxygen-condition-specific protein composition of extracellular vesicles (EVs) released from human pulmonary microvascular endothelial cells in vitro to decipher their potential role in biotrauma using quantitative proteomics with bioinformatic evaluation, transmission electron microscopy, flow cytometry, and non-activated thromboelastometry (NATEM). The release of vesicles enriched in markers CD9/CD63/CD81 was enhanced under intermittent hypoxia, strong hyperoxia and intermittent hypoxia/hyperoxia. Particles with exposed phosphatidylserine were increased under intermittent hypoxia. A small portion of vesicles were tissue factor-positive, which was enhanced under intermittent hypoxia and intermittent hypoxia/hyperoxia. EVs from treatment with intermittent hypoxia induced a significant reduction of Clotting Time in NATEM analysis compared to EVs isolated after normoxic exposure, while after intermittent hypoxia/hyperoxia, tissue factor in EVs seems to be inactive. Gene set enrichment analysis of differentially expressed genes revealed that EVs from individual oxygen conditions potentially induce different biological processes such as an inflammatory response under strong hyperoxia and intermittent hypoxia/hyperoxia and enhancement of tumor invasiveness under intermittent hypoxia.
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spelling doaj.art-eb756da830764462be0b7a884147e7ff2024-02-23T15:20:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-02-01254241510.3390/ijms25042415The Proteome of Extracellular Vesicles Released from Pulmonary Microvascular Endothelium Reveals Impact of Oxygen Conditions on BiotraumaWolfgang Schaubmayr0Beatrix Hochreiter1Eva Hunyadi-Gulyas2Louise Riegler3Katy Schmidt4Akos Tiboldi5Bernhard Moser6Klaus U. Klein7Katharina Krenn8Gisela Scharbert9Thomas Mohr10Johannes A. Schmid11Andreas Spittler12Verena Tretter13Department of Anesthesia, General Intensive Care and Pain Medicine, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Anesthesia, General Intensive Care and Pain Medicine, Medical University of Vienna, 1090 Vienna, AustriaLaboratory of Proteomics Research, HUN-REN Biological Research Centre, 6726 Szeged, HungaryDepartment of Orthopedics and Trauma Surgery, Medical University of Vienna, 1090 Vienna, AustriaCore Facility of Cell Imaging and Ultrastructure Research, University of Vienna, 1090 Vienna, AustriaDepartment of Anesthesia, General Intensive Care and Pain Medicine, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Anesthesia, General Intensive Care and Pain Medicine, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Anesthesia, General Intensive Care and Pain Medicine, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Anesthesia, General Intensive Care and Pain Medicine, Medical University of Vienna, 1090 Vienna, AustriaInstitute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, AustriaInstitute of Vascular Biology and Thrombosis Research, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Surgery and Core Facility Flow Cytometry, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Anesthesia, General Intensive Care and Pain Medicine, Medical University of Vienna, 1090 Vienna, AustriaThe lung can experience different oxygen concentrations, low as in hypoxia, high as under supplemental oxygen therapy, or oscillating during intermittent hypoxia as in obstructive sleep apnea or intermittent hypoxia/hyperoxia due to cyclic atelectasis in the ventilated patient. This study aimed to characterize the oxygen-condition-specific protein composition of extracellular vesicles (EVs) released from human pulmonary microvascular endothelial cells in vitro to decipher their potential role in biotrauma using quantitative proteomics with bioinformatic evaluation, transmission electron microscopy, flow cytometry, and non-activated thromboelastometry (NATEM). The release of vesicles enriched in markers CD9/CD63/CD81 was enhanced under intermittent hypoxia, strong hyperoxia and intermittent hypoxia/hyperoxia. Particles with exposed phosphatidylserine were increased under intermittent hypoxia. A small portion of vesicles were tissue factor-positive, which was enhanced under intermittent hypoxia and intermittent hypoxia/hyperoxia. EVs from treatment with intermittent hypoxia induced a significant reduction of Clotting Time in NATEM analysis compared to EVs isolated after normoxic exposure, while after intermittent hypoxia/hyperoxia, tissue factor in EVs seems to be inactive. Gene set enrichment analysis of differentially expressed genes revealed that EVs from individual oxygen conditions potentially induce different biological processes such as an inflammatory response under strong hyperoxia and intermittent hypoxia/hyperoxia and enhancement of tumor invasiveness under intermittent hypoxia.https://www.mdpi.com/1422-0067/25/4/2415pulmonary endotheliumoxygenextracellular vesiclestissue factorangiotensin-converting enzymevesicle proteomics
spellingShingle Wolfgang Schaubmayr
Beatrix Hochreiter
Eva Hunyadi-Gulyas
Louise Riegler
Katy Schmidt
Akos Tiboldi
Bernhard Moser
Klaus U. Klein
Katharina Krenn
Gisela Scharbert
Thomas Mohr
Johannes A. Schmid
Andreas Spittler
Verena Tretter
The Proteome of Extracellular Vesicles Released from Pulmonary Microvascular Endothelium Reveals Impact of Oxygen Conditions on Biotrauma
International Journal of Molecular Sciences
pulmonary endothelium
oxygen
extracellular vesicles
tissue factor
angiotensin-converting enzyme
vesicle proteomics
title The Proteome of Extracellular Vesicles Released from Pulmonary Microvascular Endothelium Reveals Impact of Oxygen Conditions on Biotrauma
title_full The Proteome of Extracellular Vesicles Released from Pulmonary Microvascular Endothelium Reveals Impact of Oxygen Conditions on Biotrauma
title_fullStr The Proteome of Extracellular Vesicles Released from Pulmonary Microvascular Endothelium Reveals Impact of Oxygen Conditions on Biotrauma
title_full_unstemmed The Proteome of Extracellular Vesicles Released from Pulmonary Microvascular Endothelium Reveals Impact of Oxygen Conditions on Biotrauma
title_short The Proteome of Extracellular Vesicles Released from Pulmonary Microvascular Endothelium Reveals Impact of Oxygen Conditions on Biotrauma
title_sort proteome of extracellular vesicles released from pulmonary microvascular endothelium reveals impact of oxygen conditions on biotrauma
topic pulmonary endothelium
oxygen
extracellular vesicles
tissue factor
angiotensin-converting enzyme
vesicle proteomics
url https://www.mdpi.com/1422-0067/25/4/2415
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