Moderate hyperoxia induces inflammation, apoptosis and necrosis in human umbilical vein endothelial cells: An in-vitro study

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BACKGROUNDPerioperative oxygen (O2) therapy can cause hyperoxia. Extreme hyperoxia can injure the cardiovascular system and remote organs.OBJECTIVEOur primary objective was to test the hypothesis that exposure to moderate hyperoxia will induce injury to human umbilical vein endothelial cells (HUVECs), a model for studying the vascular endothelium under controlled conditions.DESIGNIn-vitro cell culture study.SETTINGDepartment of Anaesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Austria. Study period from the beginning of October 2013 to the end of July 2014.CELLSHUVECs were isolated from fresh umbilical cords.INTERVENTIONSHUVECs were exposed to constant hyperoxia (40% O2), cyclic hyperoxia/anoxia (40%/0% O2, average 20% O2), constant normoxia (21% O2) and constant anoxia (0% O2) using a cell culture bioreactor.MAIN OUTCOME MEASURESCell growth, viability and release of IL-6, IL-8 and macrophage migration inhibitory factor were assessed at baseline and after 6, 12, 24 and 48 h of treatment. A phosphokinase array was performed after 60 min of treatment to identify activated cellular signalling pathways.RESULTSConstant hyperoxia and cyclic hyperoxia/anoxia impeded cell growth, reduced viability, triggered a proinflammatory response, proven by IL-6, IL-8 and migration inhibitory factor release, and induced apoptosis and necrosis. The inflammatory and cytotoxicity responses were highest in the constant hyperoxia group. Phosphokinase arrays revealed that different O2 concentrations activated distinct sets of cytoprotective and cell death–associated kinases, including mitogen-activated protein kinases, Src kinases, p53, Akt, mitogen-activated and stress-activated kinase, Lyn, Lck, p70S6, signal transducers and activators of transcription 5b and 6, glycogen synthase kinase 3a/b and 5′ AMP-activated protein kinases 1/2.CONCLUSIONContinuous moderate hyperoxia and cyclic moderate hyperoxia/anoxia-induced endothelial inflammation, apoptosis and necrosis. Given the large surface area of the vascular endothelium, moderately elevated O2 levels may contribute to cardiovascular inflammation and injury.TRIAL REGISTRATIONThis in-vitro study was not registered in a database.

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