Watson, O., Novodvorsky, P., Gray, C. et al. (8 more authors) (2013) Blood flow suppresses vascular Notch signalling via dll4 and is required for angiogenesis in response to hypoxic signalling. Cardiovascular Research, 100 (2). 252 - 261. ISSN 0008-6363
Abstract
Aims The contribution of blood flow to angiogenesis is incompletely understood. We examined the effect of blood flow on Notch signalling in the vasculature of zebrafish embryos, and whether blood flow regulates angiogenesis in zebrafish with constitutively up-regulated hypoxic signalling.
Methods and results Developing zebrafish (Danio rerio) embryos survive via diffusion in the absence of circulation induced by knockdown of cardiac troponin T2 or chemical cardiac cessation. The absence of blood flow increased vascular Notch signalling in 48 h post-fertilization old embryos via up-regulation of the Notch ligand dll4. Despite this, patterning of the intersegmental vessels is not affected by absent blood flow. We therefore examined homozygous vhl mutant zebrafish that have constitutively up-regulated hypoxic signalling. These display excessive and aberrant angiogenesis from 72 h post-fertilization, with significantly increased endothelial number, vessel diameter, and length. The absence of blood flow abolished these effects, though normal vessel patterning was preserved.
Conclusion We show that blood flow suppresses vascular Notch signalling via down-regulation of dll4. We have also shown that blood flow is required for angiogenesis in response to hypoxic signalling but is not required for normal vessel patterning. These data indicate important differences in hypoxia-driven vs. developmental angiogenesis.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author 2013. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
Keywords: | Zebrafish; Angiogenesis; Blood flow; Notch; Angio-/arteriogenesis |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Department of Cardiovascular Science |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 28 Sep 2015 15:58 |
Last Modified: | 28 Sep 2015 15:58 |
Published Version: | https://doi.org/http://dx.doi.org/10.1093/cvr/cvt1... |
Status: | Published |
Publisher: | Oxford University Press (OUP): Policy B - Oxford Open Option B - CC-BY |
Refereed: | Yes |
Identification Number: | 10.1093/cvr/cvt170 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:88264 |