{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T22:28:46Z","timestamp":1783549726898,"version":"3.55.0"},"reference-count":43,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"38","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2022,9,23]]},"abstract":"<jats:p>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\u2013mediated 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\u2013induced respiratory endothelial barrier disruption. We concluded that the down-regulation of CLDN5 expression is a pivotal mechanism for SARS-CoV-2\u2013induced endothelial barrier disruption in respiratory organs and that inducing CLDN5 expression is a therapeutic strategy against COVID-19.<\/jats:p>","DOI":"10.1126\/sciadv.abo6783","type":"journal-article","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T17:58:34Z","timestamp":1663783114000},"source":"Crossref","is-referenced-by-count":78,"title":["SARS-CoV-2 disrupts respiratory vascular barriers by suppressing Claudin-5 expression"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7174-4563","authenticated-orcid":true,"given":"Rina","family":"Hashimoto","sequence":"first","affiliation":[{"name":"Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, 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