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

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.

Citation

Reskiawan A. Kadir, R., Alwjwaj, M., Ahmad Othman, O., Rakkar, K., Sprigg, N., Bath, P. M., & Bayraktutan, U. (2022). Inhibition of oxidative stress delays senescence and augments functional capacity of endothelial progenitor cells. Brain Research, 1787, Article 147925. https://doi.org/10.1016/j.brainres.2022.147925

• 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