A 96-wells fluidic system for high-throughput screenings under laminar high wall shear stress conditions
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.14/42764 |
Resumo: | The ability of endothelial cells to respond to blood flow is fundamental for the correct formation and maintenance of a functional and hierarchically organized vascular network. Defective flow responses, in particular related to high flow conditions, have been associated with atherosclerosis, stroke, arteriovenous malformations, and neurodegenerative diseases. Yet, the molecular mechanisms involved in high flow response are still poorly understood. Here, we described the development and validation of a 96-wells fluidic system, with interchangeable cell culture and fluidics, to perform high-throughput screenings under laminar high-flow conditions. We demonstrated that endothelial cells in our newly developed 96-wells fluidic system respond to fluid flow-induced shear stress by aligning along the flow direction and increasing the levels of KLF2 and KLF4. We further demonstrate that our 96-wells fluidic system allows for efficient gene knock-down compatible with automated liquid handling for high-throughput screening platforms. Overall, we propose that this modular 96-well fluidic system is an excellent platform to perform genome-wide and/or drug screenings to identify the molecular mechanisms involved in the responses of endothelial cells to high wall shear stress. [Figure not available: see fulltext.]. |
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A 96-wells fluidic system for high-throughput screenings under laminar high wall shear stress conditionsThe ability of endothelial cells to respond to blood flow is fundamental for the correct formation and maintenance of a functional and hierarchically organized vascular network. Defective flow responses, in particular related to high flow conditions, have been associated with atherosclerosis, stroke, arteriovenous malformations, and neurodegenerative diseases. Yet, the molecular mechanisms involved in high flow response are still poorly understood. Here, we described the development and validation of a 96-wells fluidic system, with interchangeable cell culture and fluidics, to perform high-throughput screenings under laminar high-flow conditions. We demonstrated that endothelial cells in our newly developed 96-wells fluidic system respond to fluid flow-induced shear stress by aligning along the flow direction and increasing the levels of KLF2 and KLF4. We further demonstrate that our 96-wells fluidic system allows for efficient gene knock-down compatible with automated liquid handling for high-throughput screening platforms. Overall, we propose that this modular 96-well fluidic system is an excellent platform to perform genome-wide and/or drug screenings to identify the molecular mechanisms involved in the responses of endothelial cells to high wall shear stress. [Figure not available: see fulltext.].Veritati - Repositório Institucional da Universidade Católica PortuguesaFonseca, Catarina GonçalvesSilvério, VâniaBarata, DavidGiese, WolfgangGerhardt, HolgerCardoso, SusanaFranco, Cláudio Areias2023-10-04T13:12:41Z2023-122023-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.14/42764eng2055-743410.1038/s41378-023-00589-x85171343778PMC1050406937719414001068208100001info: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:RCAAP2023-10-24T01:34:11Zoai:repositorio.ucp.pt:10400.14/42764Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:34:05.914925Repositório 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 |
A 96-wells fluidic system for high-throughput screenings under laminar high wall shear stress conditions |
title |
A 96-wells fluidic system for high-throughput screenings under laminar high wall shear stress conditions |
spellingShingle |
A 96-wells fluidic system for high-throughput screenings under laminar high wall shear stress conditions Fonseca, Catarina Gonçalves |
title_short |
A 96-wells fluidic system for high-throughput screenings under laminar high wall shear stress conditions |
title_full |
A 96-wells fluidic system for high-throughput screenings under laminar high wall shear stress conditions |
title_fullStr |
A 96-wells fluidic system for high-throughput screenings under laminar high wall shear stress conditions |
title_full_unstemmed |
A 96-wells fluidic system for high-throughput screenings under laminar high wall shear stress conditions |
title_sort |
A 96-wells fluidic system for high-throughput screenings under laminar high wall shear stress conditions |
author |
Fonseca, Catarina Gonçalves |
author_facet |
Fonseca, Catarina Gonçalves Silvério, Vânia Barata, David Giese, Wolfgang Gerhardt, Holger Cardoso, Susana Franco, Cláudio Areias |
author_role |
author |
author2 |
Silvério, Vânia Barata, David Giese, Wolfgang Gerhardt, Holger Cardoso, Susana Franco, Cláudio Areias |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Veritati - Repositório Institucional da Universidade Católica Portuguesa |
dc.contributor.author.fl_str_mv |
Fonseca, Catarina Gonçalves Silvério, Vânia Barata, David Giese, Wolfgang Gerhardt, Holger Cardoso, Susana Franco, Cláudio Areias |
description |
The ability of endothelial cells to respond to blood flow is fundamental for the correct formation and maintenance of a functional and hierarchically organized vascular network. Defective flow responses, in particular related to high flow conditions, have been associated with atherosclerosis, stroke, arteriovenous malformations, and neurodegenerative diseases. Yet, the molecular mechanisms involved in high flow response are still poorly understood. Here, we described the development and validation of a 96-wells fluidic system, with interchangeable cell culture and fluidics, to perform high-throughput screenings under laminar high-flow conditions. We demonstrated that endothelial cells in our newly developed 96-wells fluidic system respond to fluid flow-induced shear stress by aligning along the flow direction and increasing the levels of KLF2 and KLF4. We further demonstrate that our 96-wells fluidic system allows for efficient gene knock-down compatible with automated liquid handling for high-throughput screening platforms. Overall, we propose that this modular 96-well fluidic system is an excellent platform to perform genome-wide and/or drug screenings to identify the molecular mechanisms involved in the responses of endothelial cells to high wall shear stress. [Figure not available: see fulltext.]. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-10-04T13:12:41Z 2023-12 2023-12-01T00:00:00Z |
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/10400.14/42764 |
url |
http://hdl.handle.net/10400.14/42764 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2055-7434 10.1038/s41378-023-00589-x 85171343778 PMC10504069 37719414 001068208100001 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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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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1799133606272040960 |