Show simple item record

Files in this item

Thumbnail

Item metadata

dc.contributor.authorWatson, Oliver
dc.contributor.authorNovodvorsky, Peter
dc.contributor.authorGray, Caroline
dc.contributor.authorRothman, Alexander M. K.
dc.contributor.authorLawrie, Allan
dc.contributor.authorCrossman, David C.
dc.contributor.authorHaase, Andrea
dc.contributor.authorMcMahon, Kathryn
dc.contributor.authorGering, Martin
dc.contributor.authorVan Eeden, Fredericus J. M.
dc.contributor.authorChico, Timothy J. A.
dc.date.accessioned2015-08-07T15:40:03Z
dc.date.available2015-08-07T15:40:03Z
dc.date.issued2013-11-01
dc.identifier207746795
dc.identifierf3e4af2a-a4cc-43f6-8680-2257ec406e46
dc.identifier000326015200011
dc.identifier84885967027
dc.identifier.citationWatson , O , Novodvorsky , P , Gray , C , Rothman , A M K , Lawrie , A , Crossman , D C , Haase , A , McMahon , K , Gering , M , Van Eeden , F J M & Chico , T J A 2013 , ' Blood flow suppresses vascular Notch signalling via dll4 and is required for angiogenesis in response to hypoxic signalling ' , Cardiovascular Research , vol. 100 , no. 2 , pp. 252-261 . https://doi.org/10.1093/cvr/cvt170en
dc.identifier.issn0008-6363
dc.identifier.otherORCID: /0000-0003-4762-8623/work/60196623
dc.identifier.urihttps://hdl.handle.net/10023/7155
dc.descriptionThis work was supported by BHF project grants (09/287/28051 and 12/12/ 29433) awarded to T.J.A.C. F.J.M.E. was supported by EC-FP7 HEALTHF4-2010-242048. MRC Centre Grant (G0700091) awarded to Professor PW Ingham provided a clinical training fellowship to OJW. Funding for Open Access was provided by he research was funded by the British Heart Foundation.en
dc.description.abstractThe 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. 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. 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.
dc.format.extent10
dc.format.extent1458394
dc.language.isoeng
dc.relation.ispartofCardiovascular Researchen
dc.subjectZebrafishen
dc.subjectAngiogenesisen
dc.subjectBlood flowen
dc.subjectNotchen
dc.subjectAngio-/arteriogenesisen
dc.subjectR Medicineen
dc.subject.lccRen
dc.titleBlood flow suppresses vascular Notch signalling via dll4 and is required for angiogenesis in response to hypoxic signallingen
dc.typeJournal articleen
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.contributor.institutionUniversity of St Andrews. Office of the Principalen
dc.identifier.doi10.1093/cvr/cvt170
dc.description.statusPeer revieweden


This item appears in the following Collection(s)

Show simple item record