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Hypoxia alters the expression of ACE2 and TMPRSS2 SARS-CoV-2 cell entry mediators in hCMEC/D3 brain endothelial cells.
Imperio, Guinever E; Lye, Phetcharawan; Mughis, Hafsah; Hamada, Hirotaka; Bloise, Enrrico; Lye, Stephen J; Matthews, Stephen G.
  • Imperio GE; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada. Electronic address: guinever.imperio@mail.utoronto.ca.
  • Lye P; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada; Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
  • Mughis H; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada; Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
  • Hamada H; Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
  • Bloise E; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada; Department of Physiology, University of Toronto, Toronto, Ontario, Canada; Department of Morphology, Federal University of Minas Gerais, Belo Horizonte, Brazil.
  • Lye SJ; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada; Department of Physiology, University of Toronto, Toronto, Ontario, Canada; Department of Obstetrics and Gynecology and Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
  • Matthews SG; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada; Department of Physiology, University of Toronto, Toronto, Ontario, Canada; Department of Obstetrics and Gynecology and Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Microvasc Res ; 138: 104232, 2021 11.
Artigo em Inglês | MEDLINE | ID: covidwho-1446976
ABSTRACT
The mechanisms by which the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) induces neurological complications remain to be elucidated. We aimed to identify possible effects of hypoxia on the expression of SARS-CoV-2 cell entry mediators, angiotensin-converting enzyme 2 (ACE2) receptor and transmembrane protease serine 2 (TMPRSS2) protein, in human brain endothelial cells, in vitro. hCMEC/D3 cells were exposed to different oxygen tensions 20% (Control group), 8% or 2% O2 (Hypoxia groups). Cells were harvested 6-, 24- and 48 h following hypoxic challenge for assessment of mRNA and protein, using qPCR and Western Blot. The response of the brain endothelial cells to hypoxia was replicated using modular incubator chambers. We observed an acute increase (6 h, p < 0.05), followed by a longer-term decrease (48 h, p < 0.05) in ACE2 mRNA and protein expression, accompanied by reduced expression of TMPRSS2 protein levels (48 h, p < 0.05) under the more severe hypoxic condition (2% O2). No changes in levels of von Willebrand Factor (vWF - an endothelial cell damage marker) or interleukin 6 (IL-6 - a pro-inflammatory cytokine) mRNA were observed. We conclude that hypoxia regulates brain endothelial cell ACE2 and TMPRSS2 expression in vitro, which may indicate human brain endothelial susceptibility to SARS-CoV-2 infection and subsequent brain sequelae.
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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Encéfalo / Serina Endopeptidases / Células Endoteliais / Internalização do Vírus / Enzima de Conversão de Angiotensina 2 / SARS-CoV-2 / COVID-19 Tipo de estudo: Estudo experimental / Ensaios controlados aleatorizados Tópicos: Covid persistente Limite: Humanos Idioma: Inglês Revista: Microvasc Res Ano de publicação: 2021 Tipo de documento: Artigo

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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Encéfalo / Serina Endopeptidases / Células Endoteliais / Internalização do Vírus / Enzima de Conversão de Angiotensina 2 / SARS-CoV-2 / COVID-19 Tipo de estudo: Estudo experimental / Ensaios controlados aleatorizados Tópicos: Covid persistente Limite: Humanos Idioma: Inglês Revista: Microvasc Res Ano de publicação: 2021 Tipo de documento: Artigo