PUBLICATION
Pharmacologically induced angiogenesis in transgenic zebrafish
- Authors
- Raghunath, M., Wong, Y.S., Farooq, M., and Ge, R.
- ID
- ZDB-PUB-081218-11
- Date
- 2009
- Source
- Biochemical and Biophysical Research Communications 378(4): 766-771 (Journal)
- Registered Authors
- Ge, Ruowen
- Keywords
- Zebrafish, Fli1, Neovascularisation, Prolyl hydroxylase inhibitors, Hypoxia-induced factor-1α, Drug screening, Collagen, Subintestinal vessels
- MeSH Terms
-
- Animals
- Procollagen-Proline Dioxygenase/antagonists & inhibitors*
- Pyridines/pharmacology*
- Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
- Models, Animal
- Blood Vessels/growth & development
- Cell Line
- Drug Evaluation, Preclinical/methods
- Enzyme Inhibitors/pharmacology*
- Humans
- Angiogenesis Inducing Agents/isolation & purification
- Angiogenesis Inducing Agents/pharmacology
- Collagen/metabolism
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/enzymology
- Proto-Oncogene Protein c-fli-1/genetics
- Zebrafish*/embryology
- Zebrafish*/genetics
- Zebrafish*/physiology
- Fibroblasts/drug effects
- Fibroblasts/enzymology
- Neovascularization, Physiologic/drug effects*
- Vascular Endothelial Growth Factor A/pharmacology
- Animals, Genetically Modified
- Green Fluorescent Proteins/genetics
- Hydralazine/pharmacology*
- PubMed
- 19068208 Full text @ Biochem. Biophys. Res. Commun.
Citation
Raghunath, M., Wong, Y.S., Farooq, M., and Ge, R. (2009) Pharmacologically induced angiogenesis in transgenic zebrafish. Biochemical and Biophysical Research Communications. 378(4):766-771.
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-1alpha prolyl hydroxylase. This stabilises hypoxia inducible factor-1alpha 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 6hpf to 72hpf 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping