On the preservation of vessel bifurcations during flow-mediated angiogenic remodelling

Detalhes bibliográficos
Autor(a) principal: Edgar, Lowell T.
Data de Publicação: 2021
Outros Autores: Franco, Claudio, Gerhardt, Holger, Bernabeu, Miguel O.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/49207
Resumo: Copyright: © 2021 Edgar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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spelling On the preservation of vessel bifurcations during flow-mediated angiogenic remodellingCopyright: © 2021 Edgar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.During developmental angiogenesis, endothelial cells respond to shear stress by migrating and remodelling the initially hyperbranched plexus, removing certain vessels whilst maintaining others. In this study, we argue that the key regulator of vessel preservation is cell decision behaviour at bifurcations. At flow-convergent bifurcations where migration paths diverge, cells must finely tune migration along both possible paths if the bifurcation is to persist. Experiments have demonstrated that disrupting the cells’ ability to sense shear or the junction forces transmitted between cells impacts the preservation of bifurcations during the remodelling process. However, how these migratory cues integrate during cell decision making remains poorly understood. Therefore, we present the first agent-based model of endothelial cell flow-mediated migration suitable for interrogating the mechanisms behind bifurcation stability. The model simulates flow in a bifurcated vessel network composed of agents representing endothelial cells arranged into a lumen which migrate against flow. Upon approaching a bifurcation where more than one migration path exists, agents refer to a stochastic bifurcation rule which models the decision cells make as a combination of flow-based and collective-based migratory cues. With this rule, cells favour branches with relatively larger shear stress or cell number. We found that cells must integrate both cues nearly equally to maximise bifurcation stability. In simulations with stable bifurcations, we found competitive oscillations between flow and collective cues, and simulations that lost the bifurcation were unable to maintain these oscillations. The competition between these two cues is haemodynamic in origin, and demonstrates that a natural defence against bifurcation loss during remodelling exists: as vessel lumens narrow due to cell efflux, resistance to flow and shear stress increases, attracting new cells to enter and rescue the vessel from regression. Our work provides theoretical insight into the role of junction force transmission has in stabilising vasculature during remodelling and as an emergent mechanism to avoid functional shunting.L.T.E, C.A.F, H.G., and M.O.B. would like to graciously acknowledge our funding as part of a Foundation Leducq Transatlantic Network of Excellence (17 CVD 03, https://www.mdc-berlin.de/leducq-attract). M.O.B is supported by grants from EPSRC (EP/R029598/1, EP/R021600/1). C.A.F was supported by European Research Council starting grant (679368), the Fundação para a Ciência e a Tecnologia funding (grants: PTDC/MED-PAT/31639/2017; PTDC/BIA-CEL/32180/2017; CEECIND/04251/2017). C.A.F. and M.O.B are supported by a grant from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 801423. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.PLOSRepositório da Universidade de LisboaEdgar, Lowell T.Franco, ClaudioGerhardt, HolgerBernabeu, Miguel O.2021-07-29T13:12:24Z20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/49207engPLoS Comput Biol 17(2): e1007715.1553-734X10.1371/journal.pcbi.10077151553-7358info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:52:41Zoai:repositorio.ul.pt:10451/49207Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:00:49.537241Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv On the preservation of vessel bifurcations during flow-mediated angiogenic remodelling
title On the preservation of vessel bifurcations during flow-mediated angiogenic remodelling
spellingShingle On the preservation of vessel bifurcations during flow-mediated angiogenic remodelling
Edgar, Lowell T.
title_short On the preservation of vessel bifurcations during flow-mediated angiogenic remodelling
title_full On the preservation of vessel bifurcations during flow-mediated angiogenic remodelling
title_fullStr On the preservation of vessel bifurcations during flow-mediated angiogenic remodelling
title_full_unstemmed On the preservation of vessel bifurcations during flow-mediated angiogenic remodelling
title_sort On the preservation of vessel bifurcations during flow-mediated angiogenic remodelling
author Edgar, Lowell T.
author_facet Edgar, Lowell T.
Franco, Claudio
Gerhardt, Holger
Bernabeu, Miguel O.
author_role author
author2 Franco, Claudio
Gerhardt, Holger
Bernabeu, Miguel O.
author2_role author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Edgar, Lowell T.
Franco, Claudio
Gerhardt, Holger
Bernabeu, Miguel O.
description Copyright: © 2021 Edgar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
publishDate 2021
dc.date.none.fl_str_mv 2021-07-29T13:12:24Z
2021
2021-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/49207
url http://hdl.handle.net/10451/49207
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv PLoS Comput Biol 17(2): e1007715.
1553-734X
10.1371/journal.pcbi.1007715
1553-7358
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv PLOS
publisher.none.fl_str_mv PLOS
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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