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Low oxygen tension primes aortic endothelial cells to the reparative effect of tissue-protective cytokines

journal contribution
posted on 2023-06-08, 23:12 authored by Lamia Heikal, Pietro Ghezzi, Manuela MengozziManuela Mengozzi, Gordon FernsGordon Ferns
Erythropoietin (EPO) has both erythropoietic and tissue-protective properties. The EPO analogues carbamylated EPO (CEPO) and pyroglutamate helix B surface peptide (pHBSP) lack the erythropoietic activity of EPO but retain the tissue-protective properties that are mediated by a heterocomplex of EPO receptor (EPOR) and the ß common receptor (ßCR). We studied the action of EPO and its analogues in a model of wound healing where a bovine aortic endothelial cells (BAECs) monolayer was scratched and the scratch closure was assessed over 24 h under different oxygen concentrations. We related the effects of EPO and its analogues on repair to their effect on BAECs proliferation and migration (evaluated using a micro-Boyden chamber). EPO, CEPO and pHBSP enhanced scratch closure only at lower oxygen (5%), while their effect at atmospheric oxygen (21%) was not significant. The mRNA expression of EPOR was doubled in 5% compared to 21% oxygen, and this was associated with increased EPOR assessed by immunofluorescence and Western blot. By contrast ßCR mRNA levels were similar in 5% and 21% oxygen. EPO and its analogues increased both BAECs proliferation and migration, suggesting that both may be involved in the reparative process. The priming effect of low oxygen tension on the action of tissue-protective cytokines may be of relevance to vascular disease, including atherogenesis and restenosis.

History

Publication status

  • Published

File Version

  • Published version

Journal

Molecular Medicine

ISSN

1076-1551

Publisher

Feinstein Institute for Medical Research

Issue

1

Volume

21

Page range

709-716

Department affiliated with

  • Clinical and Experimental Medicine Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2015-11-27

First Open Access (FOA) Date

2016-01-13

First Compliant Deposit (FCD) Date

2016-01-13

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