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Erschienen in: Sleep and Breathing 3/2019

25.01.2019 | Basic Science • Original Article

Blocking C/EBP β protects vascular endothelial cells from injury induced by intermittent hypoxia

verfasst von: Yu Feng, Qingchu Li, Yinxiang Wu, Nana Zhao, Lu Li, Li Li, Liming Zhao

Erschienen in: Sleep and Breathing | Ausgabe 3/2019

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Abstract

Background

Intermittent hypoxia (IH) can damage endothelial cells and lead to apoptosis in obstructive sleep apnea-hypopnea syndrome (OSAHS). Hypoxia induces apoptosis in endothelial cells via upregulation of endothelin-1 (ET-1) and hypoxia inducible factor-1 alpha (HIF-1α) plays a key role in the hypoxic stress response.

Purpose

We investigated an approach to diminish the negative effect of HIF-1α while maintaining its protective effect.

Methods

Human umbilical vein endothelial cells (HUVECs) were subjected to sustained hypoxia (SH) or IH for 24 h, and the responses of HIF-1α, CCAAT/enhancer binding protein beta (C/EBP β), and endothelin-1 (ET-1) were assessed by western blotting. A luciferase reporter system was employed to verify the potential binding site (transcription factor binding site, TFBS) for C/EBP β in the ET-1 promoter. The specificity of regulation of ET-1 by HIF-1α via C/EBP β was evaluated by a lentiviral system. The effects of silencing of C/EBP β on IH-induced apoptosis, vascular endothelial growth factor (VEGF) protein levels, proliferation, and in vitro tube formation were studied.

Results

We found that IH significantly increased HIF-1α, C/EBP β, and ET-1 in HUVECs. Knockdown of HIF-1α or C/EBP β inhibited the upregulation of ET-1 induced by IH. Blocking C/EBP β impaired IH-induced apoptosis but did not affect VEGF expression, proliferation, or in vitro tube formation. C/EBP β was shown to mediate increased ET-1 transcription by HIF-1α through the TFBS, 5′-GTTGCCTGTTG-3′, in ET-1 promoter.

Conclusion

Silencing of C/EBP β can suppress apoptosis but does not affect the protective role of HIF-1α in the hypoxic stress response.
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Metadaten
Titel
Blocking C/EBP β protects vascular endothelial cells from injury induced by intermittent hypoxia
verfasst von
Yu Feng
Qingchu Li
Yinxiang Wu
Nana Zhao
Lu Li
Li Li
Liming Zhao
Publikationsdatum
25.01.2019
Verlag
Springer International Publishing
Erschienen in
Sleep and Breathing / Ausgabe 3/2019
Print ISSN: 1520-9512
Elektronische ISSN: 1522-1709
DOI
https://doi.org/10.1007/s11325-018-1759-7

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