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Inhibition of oxidative stress delays senescence and augments functional capacity of endothelial progenitor cells

Reskiawan A. Kadir, Rais; Alwjwaj, Mansour; Ahmad Othman, Othman; Rakkar, Kamini; Sprigg, Nikola; Bath, Philip M.; Bayraktutan, Ulvi

Inhibition of oxidative stress delays senescence and augments functional capacity of endothelial progenitor cells Thumbnail


Authors

Rais Reskiawan A. Kadir

Mansour Alwjwaj

Othman Ahmad Othman

Kamini Rakkar

NIKOLA SPRIGG nikola.sprigg@nottingham.ac.uk
Professor of Stroke Medicine

Philip M. Bath



Abstract

Ageing is characterised by a progressive loss of vascular endothelial function and integrity. Endothelial progenitor cells (EPCs) play an integral role in endothelial regeneration but are prone to age-dependent changes which may accelerate their senescence and diminish their availability and functionality. Considering these, we firstly investigated the quantity of circulating EPCs in older (73.3 ± 7.2 years) and younger (40.2 ± 14.3 years) healthy volunteers and showed sharp declines in the number of EPCs expressing stemness markers (CD34 + and/or CD133 + ) in older people. These coincided with the decreases in total anti-oxidant capacity (TAC) and concomitant increases in plasma levels of pro-inflammatory cytokine, TNF-α and anti-angiogenic factor, endostatin and thrombospondin-1. The subsequent experimental studies to scrutinise the effect of ageing on molecular and functional properties of outgrowth endothelial cells (OECs), the functional subtype of EPCs, showed that chronological ageing, mimicked by replicative senescence, profoundly impaired proliferation, migration, tubulogenesis, and blood–brain barrier (BBB)-forming capacity of these cells. Similar to those seen in the clinical observational studies, senescent OECs also manifested decreased TAC and increased pro-oxidant NADPH oxidase activity and endostatin level. Suppressing oxidative stress level using structurally and functionally distinct anti-oxidants, namely vitamin C or VAS2870, an NADPH oxidase inhibitor, delayed OEC senescence and restored their tubulogenic and BBB-forming capacities. In conclusion, the enhanced oxidative stress level that develops during physiological ageing may promote EPC senescence and evoke endothelial dysfunction. Effective control of oxidative stress using either compound somewhat delays both phenomena and augments EPC functionality.

Journal Article Type Article
Acceptance Date Apr 19, 2022
Online Publication Date Apr 22, 2022
Publication Date Jul 15, 2022
Deposit Date Apr 27, 2022
Publicly Available Date Apr 23, 2023
Journal Brain Research
Print ISSN 0006-8993
Electronic ISSN 1872-6240
Publisher Elsevier BV
Peer Reviewed Peer Reviewed
Volume 1787
Article Number 147925
DOI https://doi.org/10.1016/j.brainres.2022.147925
Keywords Developmental Biology; Neurology (clinical); Molecular Biology; General Neuroscience
Public URL https://nottingham-repository.worktribe.com/output/7835545
Publisher URL https://www.sciencedirect.com/science/article/pii/S0006899322001494?via%3Dihub

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