Cyclic and constant hyperoxia cause inflammation, apoptosis and cell death in human umbilical vein endothelial cells

Wu, Jing; Hafner, Christina; Schramel, Johannes P.; Kaun, Christoph; Krychtiuk, Konstantin A.; Wojta, Johann; Boehme, Stefan; Ullrich, Robert C.; Tretter, Eva Verena; Markstaller, Klaus; Klein, Klaus Ulrich

doi:10.1111/aas.12646

Cited by 19 publications

(19 citation statements)

References 41 publications

(79 reference statements)

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“…Exposure for 72 h decreased total cell numbers back towards seeding densities, indicating cell death. The toxic effects of extreme hyperoxia were also shown in a recent study which exposed human umbilical endothelial cells (HUVEC) to 95% O 2 [52]. This study showed that the total number of cells remained equal after 8 h of exposure, whereas the number of apoptotic and dead cells had increased.…”

Section: Discussionmentioning

confidence: 56%

The effects of hyperoxia on microvascular endothelial cell proliferation and production of vaso-active substances

Attaye

Smulders

Waard

et al. 2017

ICMx

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BackgroundHyperoxia, an arterial oxygen pressure of more than 100 mmHg or 13% O2, frequently occurs in hospitalized patients due to administration of supplemental oxygen. Increasing evidence suggests that hyperoxia induces vasoconstriction in the systemic (micro)circulation, potentially affecting organ perfusion. This study addresses effects of hyperoxia on viability, proliferative capacity, and on pathways affecting vascular tone in cultured human microvascular endothelial cells (hMVEC).MethodshMVEC of the systemic circulation were exposed to graded oxygen fractions of 20, 30, 50, and 95% O2 for 8, 24, and 72 h. These fractions correspond to 152, 228, 380, and 722 mmHg, respectively. Cell proliferation and viability was measured via a proliferation assay, peroxynitrite formation via anti-nitrotyrosine levels, endothelial nitric oxide synthase (eNOS), and endothelin-1 (ET-1) levels via q-PCR and western blot analysis.ResultsExposing hMVEC to 50 and 95% O2 for more than 24 h impaired cell viability and proliferation. Hyperoxia did not significantly affect nitrotyrosine levels, nor eNOS mRNA and protein levels, regardless of the exposure time or oxygen concentration used. Phosphorylation of eNOS at the serine 1177 (S1177) residue and ET-1 mRNA levels were also not significantly affected.ConclusionsExposure of isolated human microvascular endothelial cells to marked hyperoxia for more than 24 h decreases cell viability and proliferation. Our results do not support a role of eNOS mRNA and protein or ET-1 mRNA in the potential vasoconstrictive effects of hyperoxia on isolated hMVEC.Electronic supplementary materialThe online version of this article (doi:10.1186/s40635-017-0135-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 56%

The effects of hyperoxia on microvascular endothelial cell proliferation and production of vaso-active substances

Attaye

Smulders

Waard

et al. 2017

ICMx

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“…Various cell types are compromised when exposed to cyclic oxygen variations both in a hyperoxic and hypoxic range: both ranges trigger were shown to be associated with inflammatory response [16, 17]. Furthermore, oxidative stress may play a role for oscillations leading to intermittent hyperoxia [16, 17]. Systemic PaO 2 oscillations are also transmitted to the cerebral tissue [10].…”

Section: Discussionmentioning

confidence: 99%

“…Preclinical data suggest that the occurrence of intermitting oxygen oscillations per se might represent a trigger for remote organ failure following lung injury [6, 16–19]. The role of the tidal volume as driving force for PaO 2 oscillations, their transmission to various distant organ microcirculatory sites and particularly the kidney is yet unknown.…”

Section: Introductionmentioning

confidence: 99%

Cyclic PaO2 oscillations assessed in the renal microcirculation: correlation with tidal volume in a porcine model of lung lavage

et al. 2017

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BackgroundOscillations of the arterial partial pressure of oxygen induced by varying shunt fractions occur during cyclic alveolar recruitment within the injured lung. Recently, these were proposed as a pathomechanism that may be relevant for remote organ injury following acute respiratory distress syndrome. This study examines the transmission of oxygen oscillations to the renal tissue and their tidal volume dependency.MethodsLung injury was induced by repetitive bronchoalveolar lavage in eight anaesthetized pigs. Cyclic alveolar recruitment was provoked by high tidal volume ventilation. Oscillations of the arterial partial pressure of oxygen were measured in real-time in the macrocirculation by multi-frequency phase fluorimetry and in the renal microcirculation by combined white-light spectrometry and laser-Doppler flowmetry during tidal volume down-titration.ResultsSignificant respiratory-dependent oxygen oscillations were detected in the macrocirculation and transmitted to the renal microcirculation in a substantial extent. The amplitudes of these oscillations significantly correlate to the applied tidal volume and are minimized during down-titration.ConclusionsIn a porcine model oscillations of the arterial partial pressure of oxygen are induced by cyclic alveolar recruitment and transmitted to the renal microcirculation in a tidal volume-dependent fashion. They might play a role in organ crosstalk and remote organ damage following lung injury.

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“…Normoxia group maintained in an incubator containing 5% CO 2 , 21% O 2 and 74% N 2 , and hyperoxia group maintained in an incubator containing 5% CO 2 , 40% O 2 and 55% N 2 . Both of them were kept at 37 ℃ and 90% humidity [13,14]. Meanwhile, different concentrations of heme, blank (medium) or negative control (vehicle:20mM NaOH) were added into the culture medium according to groups.…”

Section: Hmec-1 Cell Culturementioning

confidence: 99%

Heme relieves the inhibition of proliferation, migration and angiogenesis of HMEC-1 under hyperoxia by inhibiting BACH1

Jian¹,

Mei²,

Yuan³

2020

Preprint

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Background The relatively hyperoxia inhibited vascular endothelial growth factor (VEGF) in retina is the main cause of angiogenesis retardation in phase I retinopathy of prematurity (ROP). Human retinal angiogenesis is related to the proliferation, migration and angiogenesis of microvascular endothelial cells. Previous studies have confirmed that BTB and CNC homology l (BACH1) can inhibit VEGF and angiogenesis, while heme can specifically degrade BACH1. However, the effect of heme on endothelial cells and ROP remains unknown. Methods In this report, we established a model of human microvascular endothelial cells (HMEC-1) induced by 40% hyperoxia to simulate the relatively hyperoxia of phase I ROP. Meanwhile, heme was added to investigate the effects on the growth and viability of HMEC-1. Cell counting kit 8 (CCK8) and 5-ethynyl-2′-deox-yuridine (EDU) methods were used to detect the proliferation ability. Cell scratch test and matrigel matrix glue were used to detect the migration or angiogenesis ability. Western blot and immunofluorescence methods were used to detect the relative protein expression of BACH1 and VEGF. Results The proliferation, migration and angiogenesis of HMEC-1 were inhibited under hyperoxia. Moderate heme can promote endothelial cell proliferation, while excessive can inhibit, 20 µM heme could inhibit the expression of BACH1, promote the expression of VEGF, and relieve the inhibition of proliferation, migration and angiogenesis induced by hyperoxia in HMEC-1. Conclusions 20 µM heme can relieve the inhibitory effects induced by hyperoxia, via the mechanism of promoting VEGF by inhibiting BACH1 in HMEC-1, and maybe a potential medicine for retinal angiogenesis retardation induced by relatively hyperoxia in phase I ROP.

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Cyclic and constant hyperoxia cause inflammation, apoptosis and cell death in human umbilical vein endothelial cells

Abstract: Extreme hyperoxia exposure induces inflammation, apoptosis and cell death in HUVECs. Although our findings cannot be transferred to clinical settings, results suggest that hyperoxia exposure may cause vascular injury that could play a role in determining perioperative outcome.

Cited by 19 publications

References 41 publications

The effects of hyperoxia on microvascular endothelial cell proliferation and production of vaso-active substances

The effects of hyperoxia on microvascular endothelial cell proliferation and production of vaso-active substances

Cyclic PaO2 oscillations assessed in the renal microcirculation: correlation with tidal volume in a porcine model of lung lavage

Heme relieves the inhibition of proliferation, migration and angiogenesis of HMEC-1 under hyperoxia by inhibiting BACH1

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