02704nas a2200529   4500000000100000000000100001008004100002260001500043100001900058700002000077700002200097700001700119700001700136700001900153700002000172700001700192700001700209700001900226700001800245700002000263700001700283700002100300700001900321700001800340700001900358700001600377700002200393700001700415700001900432700002300451700001900474700001700493700002000510700001900530700002100549700001700570700001800587700001500605700001900620700001900639245009000658856005500748300001300803490000600816520133800822022001402160       2022                            d  c2022-09-231 aRina Hashimoto1 aJunya Takahashi1 aKeisuke Shirakura1 aRisa Funatsu1 aKaori Kosugi1 aSayaka Deguchi1 aMasaki Yamamoto1 aYugo Tsunoda1 aMaaya Morita1 aKosuke Muraoka1 aMasato Tanaka1 aTomoaki Kanbara1 aShota Tanaka1 aShigeyuki Tamiya1 aNagisa Tokunoh1 aAtsushi Kawai1 aMasahito Ikawa1 aChikako Ono1 aKeisuke Tachibana1 aMasuo Kondoh1 aMasanori Obana1 aYoshiharu Matsuura1 aAkihiro Ohsumi1 aTakeshi Noda1 aTakuya Yamamoto1 aYasuo Yoshioka1 aYu-suke Torisawa1 aHiroshi Date1 aYasushi Fujio1 aMiki Nagao1 aKazuo Takayama1 aYoshiaki Okada00aSARS-CoV-2 disrupts respiratory vascular barriers by suppressing Claudin-5 expression  uhttps://www.science.org/doi/10.1126/sciadv.abo6783  aeabo67830 v83 aIn 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.
          , 
            Organ-on-a-chip technology elucidates the mechanism of SARS-CoV-2 infection–mediated disruption of respiratory vascular barrier.  a2375-2548