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In Vivo Imaging and Quantitation of the Host Angiogenic Response in Zebrafish Tumor Xenografts
Published on: August 14, 2019
Pharmacologically induced angiogenesis in transgenic zebrafish
Michael Raghunath1, Yuan Sy Wong, Muhammad Farooq
1Tissue Modulation Laboratory, NUS Tissue Engineering Programme, Life Science Institute, National University of Singapore, Singapore. bierm@nus.edu.sg
Biochemical and Biophysical Research Communications
|December 11, 2008
Summary
Researchers explored compounds that inhibit hypoxia-inducible factor-1alpha prolyl hydroxylase to promote blood vessel formation. Zebrafish embryos treated with these compounds showed increased neovascularization, suggesting a new approach for tissue engineering.
Area of Science:
- Biomedical Engineering
- Pharmacology
- Developmental Biology
Background:
- Rapid vascularization of biomaterials and engineered tissues is crucial for successful implantation.
- Hypoxia-inducible factor-1alpha (HIF-1α) plays a key role in regulating angiogenic gene transcription.
- Inhibiting hypoxia-inducible factor-1alpha prolyl hydroxylase stabilizes HIF-1α, promoting angiogenesis.
Purpose of the Study:
- To investigate the potential of inhibiting hypoxia-inducible factor-1alpha prolyl hydroxylase for inducing neovascularization.
- To establish a small vertebrate model for in vivo screening of pro-angiogenic compounds.
- To evaluate the efficacy of hydralazine hydrochloride and 2,4-pyridine dicarboxylic acid in promoting blood vessel formation.
Main Methods:
- Utilized (TG(Fli1:EGFP)) transgenic zebrafish embryos with fluorescent blood vessels.
- Exposed zebrafish embryos to hydralazine hydrochloride and 2,4-pyridine dicarboxylic acid via immersion from 6 to 72 hours post-fertilization.
- Confirmed HIF-stabilizing effects biochemically in human fibroblasts and via an in vitro angiogenesis co-culture model (fibroblast/HUVEC).
- Assessed cross-inhibition of collagen prolyl hydroxylase by measuring collagen secretion and content.
Main Results:
- Administration of hydralazine hydrochloride and 2,4-pyridine dicarboxylic acid induced the formation of ectopic blood vessels in the subintestinal vessel basket of zebrafish embryos.
- Biochemical assays in human fibroblasts and in vitro co-culture models confirmed the HIF-stabilizing effects of the tested compounds.
- Reduced collagen secretion by fibroblasts and decreased collagen content in zebrafish embryos indicated cross-inhibition of collagen prolyl hydroxylase.
Conclusions:
- Inhibiting hypoxia-inducible factor-1alpha prolyl hydroxylase is a viable pharmacological strategy for inducing neovascularization.
- Transgenic zebrafish embryos serve as an effective small vertebrate model for in vivo screening of pro-angiogenic compounds.
- The tested compounds demonstrate potential for enhancing vascularization in tissue engineering and regenerative medicine applications.
