Back to Journals » Hypoxia » Volume 4

Erythropoietin and a nonerythropoietic peptide analog promote aortic endothelial cell repair under hypoxic conditions: role of nitric oxide

Authors Heikal L, Ghezzi P, Mengozzi M, Stelmaszczuk B, Feelisch M, Ferns G

Received 16 January 2016

Accepted for publication 23 March 2016

Published 16 August 2016 Volume 2016:4 Pages 121—133

DOI https://doi.org/10.2147/HP.S104377

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Lucy Goodman

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Dörthe Katschinski


Video abstract presented by Lamia Heikal.

Views: 380

Lamia Heikal,1 Pietro Ghezzi,1 Manuela Mengozzi,1 Blanka Stelmaszczuk,2 Martin Feelisch,2 Gordon AA Ferns1

1Brighton and Sussex Medical School, Falmer, Brighton, 2Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital and Institute for Life Sciences, Southampton, UK


Abstract: The cytoprotective effects of erythropoietin (EPO) and an EPO-related nonerythropoietic analog, pyroglutamate helix B surface peptide (pHBSP), were investigated in an in vitro model of bovine aortic endothelial cell injury under normoxic (21% O2) and hypoxic (1% O2) conditions. The potential molecular mechanisms of these effects were also explored. Using a model of endothelial injury (the scratch assay), we found that, under hypoxic conditions, EPO and pHBSP enhanced scratch closure by promoting cell migration and proliferation, but did not show any effect under normoxic conditions. Furthermore, EPO protected bovine aortic endothelial cells from staurosporine-induced apoptosis under hypoxic conditions. The priming effect of hypoxia was associated with stabilization of hypoxia inducible factor-1α, EPO receptor upregulation, and decreased Ser-1177 phosphorylation of endothelial nitric oxide synthase (NOS); the effect of hypoxia on the latter was rescued by EPO. Hypoxia was associated with a reduction in nitric oxide (NO) production as assessed by its oxidation products, nitrite and nitrate, consistent with the oxygen requirement for endogenous production of NO by endothelial NOS. However, while EPO did not affect NO formation in normoxia, it markedly increased NO production, in a manner sensitive to NOS inhibition, under hypoxic conditions. These data are consistent with the notion that the tissue-protective actions of EPO-related cytokines in pathophysiological settings associated with poor oxygenation are mediated by NO. These findings may be particularly relevant to atherogenesis and postangioplasty restenosis.

Keywords: erythropoietin, pyroglutamate helix B surface peptide, scratch assay, proliferation, migration, apoptosis

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]