|Title:||Pharmacologically induced angiogenesis in transgenic zebrafish|
|Authors :||Raghunath, Michael|
Wong, Yuan Sy
|Published in :||Biochemical and Biophysical Research Communications|
|Publisher / Ed. Institution :||Elsevier|
|License (according to publishing contract) :||Licence according to publishing contract|
|Type of review:||Peer review (publication)|
|Subject (DDC) :||571: Physiology and related subjects |
|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 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.|
|Departement:||Life Sciences and Facility Management|
|Organisational Unit:||Institute of Chemistry and Biotechnology (ICBT)|
|Publication type:||Article in scientific journal|
|Appears in Collections:||Publikationen Life Sciences und Facility Management|
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