Dikici, S. orcid.org/0000-0001-9933-5254, Bullock, A.J. orcid.org/0000-0003-0579-3997, Yar, M. et al. (2 more authors) (2020) 2-deoxy-d-ribose (2dDR) upregulates vascular endothelial growth factor (VEGF) and stimulates angiogenesis. Microvascular Research, 131. 104035. ISSN 0026-2862
Abstract
Background: Delayed neovascularisation of tissue-engineered (TE) complex constructs is a major challenge that causes their failure post-implantation. Although significant progress has been made in the field of angiogenesis, ensuring rapid neovascularisation still remains a challenge. The use of pro-angiogenic agents is an effective approach to promote angiogenesis, and vascular endothelial growth factor (VEGF) has been widely studied both at the biological and molecular levels and is recognised as a key stimulator of angiogenesis. However, the exogenous use of VEGF in an uncontrolled manner has been shown to result in leaky, permeable and haemorrhagic vessels. Thus, researchers have been actively seeking alternative agents to upregulate VEGF production rather than exogenous use of VEGF in TE systems. We have previously revealed the potential of 2-deoxy-D-ribose (2dDR) as an alternative pro-angiogenic agent to induce angiogenesis and accelerates wound healing. However, to date, there is not any clear evidence on whether 2dDR influences the angiogenic cascade that involves VEGF.
Methods: In this study, we explored the angiogenic properties of 2dDR either by its direct application to human aortic endothelial cells (HAECs) or when released from commercially available alginate dressings and demonstrated that when 2dDR promotes angiogenesis, it also increases the VEGF production of HAECs.
Results: The VEGF quantification results suggested that VEGF production by HAECs was increased with 2dDR treatment but not with other sugars, including 2-deoxy-L-ribose (2dLR) and D-glucose (DG). The stability studies demonstrated that approximately 40–50% of the 2dDR had disappeared in the media over 14 days, either in the presence or absence of HAECs, and the reduction was higher when cells were present. The concentration of VEGF in the media also fell after day 4 associated with the reduction in 2dDR.
Conclusion: This study suggests that 2dDR (but not other sugars tested in this study) stimulates angiogenesis by increasing the production of VEGF. We conclude 2dDR appears to be a practical and effective indirect route to upregulating VEGF for several days, leading to increased angiogenesis.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 Elsevier. |
Keywords: | 2-deoxy-d-ribose (2dDR); 2-deoxy-l-ribose (2dLR); Angiogenesis; Chick chorioallantoic membrane (CAM) assay; Endothelial cells; Neovascularisation; Vascular endothelial growth factor (VEGF); d-Glucose; Alginates; Angiogenesis Inducing Agents; Animals; Cells, Cultured; Chick Embryo; Chorioallantoic Membrane; Delayed-Action Preparations; Deoxyribose; Drug Carriers; Drug Stability; Endothelial Cells; Humans; Neovascularization, Physiologic; Signal Transduction; Up-Regulation; Vascular Endothelial Growth Factor A |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Engineering (Sheffield) > School of Chemical, Materials and Biological Engineering The University of Sheffield > Faculty of Engineering (Sheffield) > Department of Materials Science and Engineering (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 13 Dec 2024 09:38 |
Last Modified: | 13 Dec 2024 09:38 |
Status: | Published |
Publisher: | Elsevier BV |
Refereed: | Yes |
Identification Number: | 10.1016/j.mvr.2020.104035 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:220780 |