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|Title:||Pharmacologically induced angiogenesis in transgenic zebrafish|
|Authors:||Raghunath, M. |
Sy Wong, Y.
Prolyl hydroxylase inhibitors
|Citation:||Raghunath, M., Sy Wong, Y., Farooq, M., Ge, R. (2009-01-23). Pharmacologically induced angiogenesis in transgenic zebrafish. Biochemical and Biophysical Research Communications 378 (4) : 766-771. ScholarBank@NUS Repository. https://doi.org/10.1016/j.bbrc.2008.11.127|
|Abstract:||The rapid vascularisation of biomaterials and engineered tissue after implantation is a current unmet need. To this end, we explored the pharmacological option of inducing neovascularisation using compounds that inhibit hypoxia-induced factor-1α prolyl hydroxylase. This stabilises hypoxia inducible factor-1α and therefore de-repress the transcription of various angiogenic genes. In the quest for a small vertebrate model allowing for in vivo screening we exposed (TG(Fli1:EGFP)) transgenic zebrafish embryos exhibiting fluorescent blood vessels to hydralazine hydrochloride and 2,4-pyridine dicarboxylic acid from 6 hpf to 72 hpf by immersion. Live observation of embryos revealed that the substances induced formation of ectopic blood vessels in the subintestinal vessel basket. We confirmed the HIF-stabilising effects biochemically in human fibroblasts and with an in vitro angiogenesis fibroblast/HUVEC co-culture model. Cross-inhibition of collagen prolyl hydroxylase was confirmed by reduced collagen secretion by fibroblasts and reduced collagen content of zebrafish embryos. © 2008 Elsevier Inc. All rights reserved.|
|Source Title:||Biochemical and Biophysical Research Communications|
|Appears in Collections:||Staff Publications|
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