Engineering a vascular endothelial growth factor 165-binding heparan sulfate for vascular therapy
The therapeutic use of VEGF165 to stimulate blood vessel formation for the treatment of peripheral arterial disease or cardiovascular-related disease has met with limited success. Here we describe an affinity-isolated heparan sulfate glycotherapeutic (HS7+ve) that binds to, and enhances the bioactiv...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2016
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| Online Access: | https://hdl.handle.net/10356/81666 http://hdl.handle.net/10220/40874 |
| _version_ | 1811685427414827008 |
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| author | Wang, Chunming Poon, Selina Murali, Sadasivam Koo, Chuay-Yeng Bell, Tracey J. Hinkley, Simon F. Yeong, Huiqing Bhakoo, Kishore Nurcombe, Victor Cool, Simon M. |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Wang, Chunming Poon, Selina Murali, Sadasivam Koo, Chuay-Yeng Bell, Tracey J. Hinkley, Simon F. Yeong, Huiqing Bhakoo, Kishore Nurcombe, Victor Cool, Simon M. |
| author_sort | Wang, Chunming |
| collection | NTU |
| description | The therapeutic use of VEGF165 to stimulate blood vessel formation for the treatment of peripheral arterial disease or cardiovascular-related disease has met with limited success. Here we describe an affinity-isolated heparan sulfate glycotherapeutic (HS7+ve) that binds to, and enhances the bioactivity of, VEGF165. Application of HS7+ve complexed with VEGF165 results in enhanced VEGF165–VEGFR2 interaction, prolonged downstream pErk1/2 signalling, and increased cell proliferation and tube formation in HUVECs, compared with VEGF165 alone. The pro-angiogenic potential of HS7+ve was further assessed in vivo using the chick embryo chorioallantoic membrane (CAM) assay. Exogenous dosing with HS7+ve alone significantly enhanced the formation of new blood vessels with potencies comparable to VEGF165. These results demonstrate the potential for vascular therapy of glycotherapeutic agents targeted at augmenting the bioactivity of VEGF165. |
| first_indexed | 2024-10-01T04:44:21Z |
| format | Journal Article |
| id | ntu-10356/81666 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:44:21Z |
| publishDate | 2016 |
| record_format | dspace |
| spelling | ntu-10356/816662020-03-07T12:57:22Z Engineering a vascular endothelial growth factor 165-binding heparan sulfate for vascular therapy Wang, Chunming Poon, Selina Murali, Sadasivam Koo, Chuay-Yeng Bell, Tracey J. Hinkley, Simon F. Yeong, Huiqing Bhakoo, Kishore Nurcombe, Victor Cool, Simon M. Lee Kong Chian School of Medicine (LKCMedicine) Angiogenesis Vasculogenesis The therapeutic use of VEGF165 to stimulate blood vessel formation for the treatment of peripheral arterial disease or cardiovascular-related disease has met with limited success. Here we describe an affinity-isolated heparan sulfate glycotherapeutic (HS7+ve) that binds to, and enhances the bioactivity of, VEGF165. Application of HS7+ve complexed with VEGF165 results in enhanced VEGF165–VEGFR2 interaction, prolonged downstream pErk1/2 signalling, and increased cell proliferation and tube formation in HUVECs, compared with VEGF165 alone. The pro-angiogenic potential of HS7+ve was further assessed in vivo using the chick embryo chorioallantoic membrane (CAM) assay. Exogenous dosing with HS7+ve alone significantly enhanced the formation of new blood vessels with potencies comparable to VEGF165. These results demonstrate the potential for vascular therapy of glycotherapeutic agents targeted at augmenting the bioactivity of VEGF165. ASTAR (Agency for Sci., Tech. and Research, S’pore) 2016-07-01T08:11:36Z 2019-12-06T14:35:49Z 2016-07-01T08:11:36Z 2019-12-06T14:35:49Z 2014 Journal Article Wang, C., Poon, S., Murali, S., Koo, C.-Y., Bell, T. J., Hinkley, S. F., et al. (2014). Engineering a vascular endothelial growth factor 165-binding heparan sulfate for vascular therapy. Biomaterials, 35(25), 6776-6786. 0142-9612 https://hdl.handle.net/10356/81666 http://hdl.handle.net/10220/40874 10.1016/j.biomaterials.2014.04.084 en Biomaterials © 2014 Elsevier. |
| spellingShingle | Angiogenesis Vasculogenesis Wang, Chunming Poon, Selina Murali, Sadasivam Koo, Chuay-Yeng Bell, Tracey J. Hinkley, Simon F. Yeong, Huiqing Bhakoo, Kishore Nurcombe, Victor Cool, Simon M. Engineering a vascular endothelial growth factor 165-binding heparan sulfate for vascular therapy |
| title | Engineering a vascular endothelial growth factor 165-binding heparan sulfate for vascular therapy |
| title_full | Engineering a vascular endothelial growth factor 165-binding heparan sulfate for vascular therapy |
| title_fullStr | Engineering a vascular endothelial growth factor 165-binding heparan sulfate for vascular therapy |
| title_full_unstemmed | Engineering a vascular endothelial growth factor 165-binding heparan sulfate for vascular therapy |
| title_short | Engineering a vascular endothelial growth factor 165-binding heparan sulfate for vascular therapy |
| title_sort | engineering a vascular endothelial growth factor 165 binding heparan sulfate for vascular therapy |
| topic | Angiogenesis Vasculogenesis |
| url | https://hdl.handle.net/10356/81666 http://hdl.handle.net/10220/40874 |
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