Human Brain Microvascular Endothelial Cells Exposure to SARS-CoV-2 Leads to Inflammatory Activation through NF- B Non-Canonical Pathway and Mitochondrial Remodeling

Detalhes bibliográficos
Autor(a) principal: Motta, Carolline Soares
Data de Publicação: 2023
Outros Autores: Torices, Silvia, Rosa, Barbara Gomes da, Marcos, Anne Caroline, Alvarez-Rosa, Liandra, Siqueira, Michele, Moreno-Rodriguez, Thaidy, Matos, Aline da Rocha, Caetano, Braulia Costa, Martins, Jessica Santa Cruz de Carvalho, Gladulich, Luis, Loiola, Erick, Bagshaw, Olivia R. M., Stuart, Jeffrey A., Siqueira, Marilda M., Stipursky, Joice, Toborek, Michal, Adesse, Daniel
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/57782
Resumo: Abstract: Neurological effects of COVID-19 and long-COVID-19, as well as neuroinvasion by SARS-CoV-2, still pose several questions and are of both clinical and scientific relevance. We described the cellular and molecular effects of the human brain microvascular endothelial cells (HBMECs) in vitro exposure by SARS-CoV-2 to understand the underlying mechanisms of viral transmigration through the blood–brain barrier. Despite the low to non-productive viral replication, SARS-CoV-2-exposed cultures displayed increased immunoreactivity for cleaved caspase-3, an indicator of apoptotic cell death, tight junction protein expression, and immunolocalization. Transcriptomic profiling of SARS-CoV-2-challenged cultures revealed endothelial activation via NF- B non-canonical pathway, including RELB overexpression and mitochondrial dysfunction. Additionally, SARS-CoV-2 led to altered secretion of key angiogenic factors and to significant changes in mitochondrial dynamics, with increased mitofusin-2 expression and increased mitochondrial networks. Endothelial activation and remodeling can further contribute to neuroinflammatory processes and lead to further BBB permeability in COVID-19.
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spelling Motta, Carolline SoaresTorices, SilviaRosa, Barbara Gomes daMarcos, Anne CarolineAlvarez-Rosa, LiandraSiqueira, MicheleMoreno-Rodriguez, ThaidyMatos, Aline da RochaCaetano, Braulia CostaMartins, Jessica Santa Cruz de CarvalhoGladulich, LuisLoiola, ErickBagshaw, Olivia R. M.Stuart, Jeffrey A.Siqueira, Marilda M.Stipursky, JoiceToborek, MichalAdesse, Daniel2023-04-14T13:42:46Z2023-04-14T13:42:46Z2023MOTTA, Caroline Soares et al. Human Brain Microvascular Endothelial Cells Exposure to SARS-CoV-2 Leads to Inflammatory Activation through NF- B Non-Canonical Pathway and Mitochondrial Remodeling. Viruses, v.15, 745, p. 1 - 25, Mar. 2023.1999-4915https://www.arca.fiocruz.br/handle/icict/5778210.3390/v15030745Abstract: Neurological effects of COVID-19 and long-COVID-19, as well as neuroinvasion by SARS-CoV-2, still pose several questions and are of both clinical and scientific relevance. We described the cellular and molecular effects of the human brain microvascular endothelial cells (HBMECs) in vitro exposure by SARS-CoV-2 to understand the underlying mechanisms of viral transmigration through the blood–brain barrier. Despite the low to non-productive viral replication, SARS-CoV-2-exposed cultures displayed increased immunoreactivity for cleaved caspase-3, an indicator of apoptotic cell death, tight junction protein expression, and immunolocalization. Transcriptomic profiling of SARS-CoV-2-challenged cultures revealed endothelial activation via NF- B non-canonical pathway, including RELB overexpression and mitochondrial dysfunction. Additionally, SARS-CoV-2 led to altered secretion of key angiogenic factors and to significant changes in mitochondrial dynamics, with increased mitofusin-2 expression and increased mitochondrial networks. Endothelial activation and remodeling can further contribute to neuroinflammatory processes and lead to further BBB permeability in COVID-19.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Estrutural. Rio de Janeiro, RJ, Brasil.Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Estrutural. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Estrutural. Rio de Janeiro, RJ, Brasil / Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Estrutural. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Laboratório Compartilhado. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Laboratório Compartilhado. Rio de Janeiro, RJ, Brasil.Urology Department, University of California San Francisco, San Francisco, CA 94143, USA / Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94143, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratórios, Exantemáticos, Enterovírus e Emergências Virais (LVRE). Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratórios, Exantemáticos, Enterovírus e Emergências Virais (LVRE). Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratórios, Exantemáticos, Enterovírus e Emergências Virais (LVRE). Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Estrutural. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Estrutural. Rio de Janeiro, RJ, Brasil.Faculty of Mathematics & Science, Brock University, St. Catharines, ON L2S 3A1, Canada.Faculty of Mathematics & Science, Brock University, St. Catharines, ON L2S 3A1, Canada.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratórios, Exantemáticos, Enterovírus e Emergências Virais (LVRE). Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Laboratório Compartilhado. Rio de Janeiro, RJ, Brasil.Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Estrutural. Rio de Janeiro, RJ, Brasil / Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.engMDPICOVID-19Barreira hematoencefalicaDinâmica mitocondrialVia de sinalização NF-BAtivação endotelialCOVID-19Blood–Brain BarrierMitochondrial dynamicsNF- B signaling pathwayEndothelial activationHuman Brain Microvascular Endothelial Cells Exposure to SARS-CoV-2 Leads to Inflammatory Activation through NF- B Non-Canonical Pathway and Mitochondrial Remodelinginfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; 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dc.title.en_US.fl_str_mv Human Brain Microvascular Endothelial Cells Exposure to SARS-CoV-2 Leads to Inflammatory Activation through NF- B Non-Canonical Pathway and Mitochondrial Remodeling
title Human Brain Microvascular Endothelial Cells Exposure to SARS-CoV-2 Leads to Inflammatory Activation through NF- B Non-Canonical Pathway and Mitochondrial Remodeling
spellingShingle Human Brain Microvascular Endothelial Cells Exposure to SARS-CoV-2 Leads to Inflammatory Activation through NF- B Non-Canonical Pathway and Mitochondrial Remodeling
Motta, Carolline Soares
COVID-19
Barreira hematoencefalica
Dinâmica mitocondrial
Via de sinalização NF-B
Ativação endotelial
COVID-19
Blood–Brain Barrier
Mitochondrial dynamics
NF- B signaling pathway
Endothelial activation
title_short Human Brain Microvascular Endothelial Cells Exposure to SARS-CoV-2 Leads to Inflammatory Activation through NF- B Non-Canonical Pathway and Mitochondrial Remodeling
title_full Human Brain Microvascular Endothelial Cells Exposure to SARS-CoV-2 Leads to Inflammatory Activation through NF- B Non-Canonical Pathway and Mitochondrial Remodeling
title_fullStr Human Brain Microvascular Endothelial Cells Exposure to SARS-CoV-2 Leads to Inflammatory Activation through NF- B Non-Canonical Pathway and Mitochondrial Remodeling
title_full_unstemmed Human Brain Microvascular Endothelial Cells Exposure to SARS-CoV-2 Leads to Inflammatory Activation through NF- B Non-Canonical Pathway and Mitochondrial Remodeling
title_sort Human Brain Microvascular Endothelial Cells Exposure to SARS-CoV-2 Leads to Inflammatory Activation through NF- B Non-Canonical Pathway and Mitochondrial Remodeling
author Motta, Carolline Soares
author_facet Motta, Carolline Soares
Torices, Silvia
Rosa, Barbara Gomes da
Marcos, Anne Caroline
Alvarez-Rosa, Liandra
Siqueira, Michele
Moreno-Rodriguez, Thaidy
Matos, Aline da Rocha
Caetano, Braulia Costa
Martins, Jessica Santa Cruz de Carvalho
Gladulich, Luis
Loiola, Erick
Bagshaw, Olivia R. M.
Stuart, Jeffrey A.
Siqueira, Marilda M.
Stipursky, Joice
Toborek, Michal
Adesse, Daniel
author_role author
author2 Torices, Silvia
Rosa, Barbara Gomes da
Marcos, Anne Caroline
Alvarez-Rosa, Liandra
Siqueira, Michele
Moreno-Rodriguez, Thaidy
Matos, Aline da Rocha
Caetano, Braulia Costa
Martins, Jessica Santa Cruz de Carvalho
Gladulich, Luis
Loiola, Erick
Bagshaw, Olivia R. M.
Stuart, Jeffrey A.
Siqueira, Marilda M.
Stipursky, Joice
Toborek, Michal
Adesse, Daniel
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Motta, Carolline Soares
Torices, Silvia
Rosa, Barbara Gomes da
Marcos, Anne Caroline
Alvarez-Rosa, Liandra
Siqueira, Michele
Moreno-Rodriguez, Thaidy
Matos, Aline da Rocha
Caetano, Braulia Costa
Martins, Jessica Santa Cruz de Carvalho
Gladulich, Luis
Loiola, Erick
Bagshaw, Olivia R. M.
Stuart, Jeffrey A.
Siqueira, Marilda M.
Stipursky, Joice
Toborek, Michal
Adesse, Daniel
dc.subject.other.en_US.fl_str_mv COVID-19
Barreira hematoencefalica
Dinâmica mitocondrial
Via de sinalização NF-B
Ativação endotelial
topic COVID-19
Barreira hematoencefalica
Dinâmica mitocondrial
Via de sinalização NF-B
Ativação endotelial
COVID-19
Blood–Brain Barrier
Mitochondrial dynamics
NF- B signaling pathway
Endothelial activation
dc.subject.en.en_US.fl_str_mv COVID-19
Blood–Brain Barrier
Mitochondrial dynamics
NF- B signaling pathway
Endothelial activation
description Abstract: Neurological effects of COVID-19 and long-COVID-19, as well as neuroinvasion by SARS-CoV-2, still pose several questions and are of both clinical and scientific relevance. We described the cellular and molecular effects of the human brain microvascular endothelial cells (HBMECs) in vitro exposure by SARS-CoV-2 to understand the underlying mechanisms of viral transmigration through the blood–brain barrier. Despite the low to non-productive viral replication, SARS-CoV-2-exposed cultures displayed increased immunoreactivity for cleaved caspase-3, an indicator of apoptotic cell death, tight junction protein expression, and immunolocalization. Transcriptomic profiling of SARS-CoV-2-challenged cultures revealed endothelial activation via NF- B non-canonical pathway, including RELB overexpression and mitochondrial dysfunction. Additionally, SARS-CoV-2 led to altered secretion of key angiogenic factors and to significant changes in mitochondrial dynamics, with increased mitofusin-2 expression and increased mitochondrial networks. Endothelial activation and remodeling can further contribute to neuroinflammatory processes and lead to further BBB permeability in COVID-19.
publishDate 2023
dc.date.accessioned.fl_str_mv 2023-04-14T13:42:46Z
dc.date.available.fl_str_mv 2023-04-14T13:42:46Z
dc.date.issued.fl_str_mv 2023
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.citation.fl_str_mv MOTTA, Caroline Soares et al. Human Brain Microvascular Endothelial Cells Exposure to SARS-CoV-2 Leads to Inflammatory Activation through NF- B Non-Canonical Pathway and Mitochondrial Remodeling. Viruses, v.15, 745, p. 1 - 25, Mar. 2023.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/57782
dc.identifier.issn.en_US.fl_str_mv 1999-4915
dc.identifier.doi.none.fl_str_mv 10.3390/v15030745
identifier_str_mv MOTTA, Caroline Soares et al. Human Brain Microvascular Endothelial Cells Exposure to SARS-CoV-2 Leads to Inflammatory Activation through NF- B Non-Canonical Pathway and Mitochondrial Remodeling. Viruses, v.15, 745, p. 1 - 25, Mar. 2023.
1999-4915
10.3390/v15030745
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collection Repositório Institucional da FIOCRUZ (ARCA)
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