Abstract
Reactive oxygen species (ROS) produced by NADPH oxidases are involved in a number of (patho)physiological processes such as stem cell function, embryogenesis, differentiation and angiogenesis. Increased ROS generation is known to lead to widespread epigenetic changes within the cell, a process which leads to transcriptional and subsequent cell biology alterations. A specific role for NADPH oxidases in the pro-angiogenic response of progenitor endothelial colony-forming cells (ECFC) is well-supported; these cells are important in revascularisation and vascular homeostasis, holding great cytotherapeutic potential for ischaemic disease. The aim of this study was to investigate the specific influence of NOX4 NADPH oxidase on ECFC angiogenic function. Human ECFCs treated with pro-oxidant phorbol 12-myristate 13-acetate (PMA) displayed: (1) increased migration and the ability to form tubes in vitro, an effect ablated when co-incubated with PMA and either superoxide dismutase or VAS2870 (NOX inhibitor); (2) upregulated NOX4 expression. Genetic depletion (RNAi; KD) resulted in attenuation of in vitro migration and tube formation, whilst in vivo, ischaemic hindlimb tissue injected with KD cells showed reduced perfusion after 14 days versus tissue treated with WT cells. These data confirm enhanced ECFC migration upon ROS production and indicate specific NOX4-dependent functionality; NOX4 over-expression may help improve ECFC angiogenic potential. Screening following NOX4 depletion and over-expression may shed light on DNA methylation and chromatin remodelling (methylation/acetylation etc) attributed specifically to NOX4-generated ROS adding to current knowledge of mechanisms underlying dynamic embryonic and stem cell differentiation processes.
Original language | English |
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Publication status | Unpublished - 01 Mar 2017 |
Event | Biotechne Epigenetics Symposium - Amsterdam, Netherlands Duration: 01 Mar 2017 → 01 Mar 2017 |
Conference
Conference | Biotechne Epigenetics Symposium |
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Country/Territory | Netherlands |
City | Amsterdam |
Period | 01/03/2017 → 01/03/2017 |
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Investigating the role of NADPH oxidase 4 (NOX4) in differentiation and function of induced pluripotent stem cell–derived endothelial cells
Moez, A. (Author), Grieve, D. (Supervisor) & Margariti, A. (Supervisor), Dec 2021Student thesis: Doctoral Thesis › Doctor of Philosophy
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