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Mechanisms of vascular endothelial cell injury in response to intermittent and/or continuous hypoxia exposure and protective effects of anti-inflammatory and anti-oxidant agents

  • Sleep Breathing Physiology and Disorders • Original Article
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Abstract

Background

Hypoxia induces vascular endothelial injuries; however, the mechanisms involved and effects of interventions remain unclear.

Objective

Investigate the inflammatory response and oxidative stress in co-cultured neutrophils and vascular endothelial cells, apoptotic changes in endothelial cells, and effects of the antioxidant, Tempol, or the NF-êB inflammatory channel blocker, pyrrolidine dithiocarbamate (PDTC), upon endothelial cells under conditions of intermittent and/or continuous hypoxic exposure.

Methods

Polymorphonuclear neutrophils co-cultured with human umbilical vein endothelial cells were subjected to the following conditions: intermittent normoxia (IN), intermittent hypoxia (IH), continuous hypoxia (CH), intermittent with continuous hypoxia (OS), OS+Tempol (OS+T), or OS+PDTC (OS+P) for 2, 5, or 8 h. Inflammatory factors, TNF-α and IL-6, the adhesion molecule, ICAM-1, CAT activity, and MDA concentrations in supernatants from the co-culture as well as pro- (Bak) and anti- (Bcl-xl) apoptotic gene expression levels in the endothelial cells were determined.

Results

Inflammatory factors, adhesion molecules, oxidative stress, and apoptosis genes in all groups showed significant, time-dependent increases as compared with the IN group. TNF-α, IL-6, ICAM-1, and MDA levels in the OS group were increased, while CAT was decreased as compared with that observed in the IH, CH, OS+T, and OS+P groups. Bcl-x1 expression and Bcl-x1/BAK ratios were decreased and BAX increased in the OS versus IH, CH, OS+T, or OS+P groups. Both pro- and anti-apoptotic proteins showed time-dependent increases, while the Bcl-x1/BAK ratio decreased over these times. Tempol and PDTC partially prevented these effects.

Conclusion

Inflammation, oxidative stress, and apoptosis are all involved in vascular endothelial injury induced by OS. Anti-inflammatory and anti-oxidative interventions can partially improve effects of OS.

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Funding

This study was funded by the National Natural Science Foundation of China (grant number 81670084).

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Author notes

  1. Fan Xiao and Xin Li contributed equally to this work.

Authors and Affiliations

  1. Department of Respiratory and Critical Care, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China

    Fan Xiao, Xin Li, Juan Wang & Jie Cao

  2. Department of Respiratory Medicine, Tianjin Third Central Hospital - Branch Hospital, 220 Jiangdu Road, Hebei District, Tianjin, 300250, China

    Fan Xiao

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  1. Fan Xiao
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  2. Xin Li
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  3. Juan Wang
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  4. Jie Cao
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Correspondence to Jie Cao.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Xiao, F., Li, X., Wang, J. et al. Mechanisms of vascular endothelial cell injury in response to intermittent and/or continuous hypoxia exposure and protective effects of anti-inflammatory and anti-oxidant agents. Sleep Breath 23, 515–522 (2019). https://doi.org/10.1007/s11325-019-01803-9

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  • DOI: https://doi.org/10.1007/s11325-019-01803-9

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