SARS-CoV-2 disrupts respiratory vascular barriers by suppressing Claudin-5 expression.
Sci Adv
; 8(38): eabo6783, 2022 09 23.
Article
in English
| MEDLINE | ID: covidwho-2038224
ABSTRACT
In the initial process of coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects respiratory epithelial cells and then transfers to other organs the blood vessels. It is believed that SARS-CoV-2 can pass the vascular wall by altering the endothelial barrier using an unknown mechanism. In this study, we investigated the effect of SARS-CoV-2 on the endothelial barrier using an airway-on-a-chip that mimics respiratory organs and found that SARS-CoV-2 produced from infected epithelial cells disrupts the barrier by decreasing Claudin-5 (CLDN5), a tight junction protein, and disrupting vascular endothelial cadherin-mediated adherens junctions. Consistently, the gene and protein expression levels of CLDN5 in the lungs of a patient with COVID-19 were decreased. CLDN5 overexpression or Fluvastatin treatment rescued the SARS-CoV-2-induced respiratory endothelial barrier disruption. We concluded that the down-regulation of CLDN5 expression is a pivotal mechanism for SARS-CoV-2-induced endothelial barrier disruption in respiratory organs and that inducing CLDN5 expression is a therapeutic strategy against COVID-19.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Claudin-5
/
SARS-CoV-2
/
COVID-19
Limits:
Humans
Language:
English
Journal:
Sci Adv
Year:
2022
Document Type:
Article
Affiliation country:
Sciadv.abo6783
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