期刊
MICROVASCULAR RESEARCH
卷 138, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mvr.2021.104232
关键词
Hypoxia; Human cerebral microvascular endothelial; cells (hCMEC; D3); Covid19; SARS-CoV-2; Angiotensin-converting enzyme 2 (ACE2); Transmembrane protease serine 2 (TMPRSS2); Blood-brain barrier (BBB)
资金
- Coordenacao de Aperfeicoamento Pessoal de Nivel Superior (CAPES) [001]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [310578/2020-5]
- Canadian Institutes of Health Research (CIHR) [FDN-143262]
- Canadian Institutes of Health Research [FDN-148368]
This study demonstrated that hypoxia can regulate the expression of ACE2 and TMPRSS2 in human brain endothelial cells, indicating potential susceptibility of the brain endothelium to SARS-CoV-2 infection.
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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