| Autor: |
Schaubmayr W; Department of Anesthesia, General Intensive Care and Pain Medicine, Medical University of Vienna, 1090 Vienna, Austria., Hochreiter B; Department of Anesthesia, General Intensive Care and Pain Medicine, Medical University of Vienna, 1090 Vienna, Austria., Hunyadi-Gulyas E; Laboratory of Proteomics Research, HUN-REN Biological Research Centre, 6726 Szeged, Hungary., Riegler L; Department of Orthopedics and Trauma Surgery, Medical University of Vienna, 1090 Vienna, Austria., Schmidt K; Core Facility of Cell Imaging and Ultrastructure Research, University of Vienna, 1090 Vienna, Austria., Tiboldi A; Department of Anesthesia, General Intensive Care and Pain Medicine, Medical University of Vienna, 1090 Vienna, Austria., Moser B; Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria., Klein KU; Department of Anesthesia, General Intensive Care and Pain Medicine, Medical University of Vienna, 1090 Vienna, Austria., Krenn K; Department of Anesthesia, General Intensive Care and Pain Medicine, Medical University of Vienna, 1090 Vienna, Austria., Scharbert G; Department of Anesthesia, General Intensive Care and Pain Medicine, Medical University of Vienna, 1090 Vienna, Austria., Mohr T; Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria., Schmid JA; Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, 1090 Vienna, Austria., Spittler A; Department of Surgery and Core Facility Flow Cytometry, Medical University of Vienna, 1090 Vienna, Austria., Tretter V; Department of Anesthesia, General Intensive Care and Pain Medicine, Medical University of Vienna, 1090 Vienna, Austria. |
| Abstrakt: |
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. |
