The University of Southampton
University of Southampton Institutional Repository

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

Erythropoietin and a nonerythropoietic peptide analog promote aortic endothelial cell repair under hypoxic conditions: role of nitric oxide
Erythropoietin and a nonerythropoietic peptide analog promote aortic endothelial cell repair under hypoxic conditions: role of nitric oxide
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-1?, 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.
121-133
Heikal, Lamia
74c311c6-1787-47fb-89ed-90980043be4b
Ghezzi, Pietro
63678bdc-0e7e-4d98-93e9-e52f2aaf5fce
Mengozzi, Manuela
f3a8bb1c-a212-4b9e-ac66-49da54b5967b
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Stelmaszczuk, Blanka
cecabbe4-5a70-4082-af49-aedd05d90af8
Ferns, Gordon A.A.
edcbb92c-968c-49b1-9316-ad00c13784c4
Heikal, Lamia
74c311c6-1787-47fb-89ed-90980043be4b
Ghezzi, Pietro
63678bdc-0e7e-4d98-93e9-e52f2aaf5fce
Mengozzi, Manuela
f3a8bb1c-a212-4b9e-ac66-49da54b5967b
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Stelmaszczuk, Blanka
cecabbe4-5a70-4082-af49-aedd05d90af8
Ferns, Gordon A.A.
edcbb92c-968c-49b1-9316-ad00c13784c4

Heikal, Lamia, Ghezzi, Pietro, Mengozzi, Manuela, Feelisch, Martin, Stelmaszczuk, Blanka and Ferns, Gordon A.A. (2016) Erythropoietin and a nonerythropoietic peptide analog promote aortic endothelial cell repair under hypoxic conditions: role of nitric oxide. Hypoxia, 4, 121-133. (doi:10.2147/HP.S104377).

Record type: Article

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-1?, 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.

Text
HP-104377-erythropoietin-and-a-non-erythropoietic-peptide-analogue-pro_081616.pdf - Version of Record
Available under License Other.
Download (2MB)

More information

Accepted/In Press date: 23 March 2016
e-pub ahead of print date: 16 August 2016
Published date: 16 August 2016
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 399854
URI: http://eprints.soton.ac.uk/id/eprint/399854
PURE UUID: 324e2ad9-dd15-4f25-9f9d-7819e2acce9a
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

Catalogue record

Date deposited: 01 Sep 2016 08:54
Last modified: 15 Mar 2024 03:42

Export record

Altmetrics

Contributors

Author: Lamia Heikal
Author: Pietro Ghezzi
Author: Manuela Mengozzi
Author: Martin Feelisch ORCID iD
Author: Blanka Stelmaszczuk
Author: Gordon A.A. Ferns

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×