SARS-CoV-2 infection promotes lung thrombosis by inducing integrinβ3 expression in vascular endothelial cells

Abstract Severe COVID-19 shows a high incidence of pulmonary thrombosis. However, the molecular mechanism underlying this phenomenon remains unclear. We have performed RNA sequencing of isolated endothelial cells (ECs) from infected mid-aged and young mice. Compared to young mice, Integrinβ3 (ITGB3)...

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Main Authors: Wataru Ito, Yuya Sakurai, Nako Maishi, Ryo Takeda, Takahito Teshirogi, Li Yu, Yasuhiro Hida, Michihito Sasaki, Yasuko Orba, Takuya Tsumita, Haruhisa Watanabe, Tadahiro Iimura, Terufumi Kubo, Shinsuke Toba, Akihiko Sato, Aya Matsuda, Daisuke Kyuno, Makoto Osanai, Yoichi Ohiro, Toshihiko Torigoe, Hirofumi Sawa, Kyoko Hida
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-02784-4
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Summary:Abstract Severe COVID-19 shows a high incidence of pulmonary thrombosis. However, the molecular mechanism underlying this phenomenon remains unclear. We have performed RNA sequencing of isolated endothelial cells (ECs) from infected mid-aged and young mice. Compared to young mice, Integrinβ3 (ITGB3) expression levels were higher in ECs of mid-aged mice which showed thrombosis in lungs. SARS-CoV-2 exposure increased the number of adhered platelets on the EC monolayer in vitro. Knockdown of ITGB3 in ECs decreased platelet adhesion to them. Among the molecules known as SARS-CoV-2 receptors, Kringle-containing transmembrane protein 1 contributed to ITGB3 upregulation in ECs by SARS-CoV-2. Histological analysis showed that ITGB3-positive blood vessels were frequently detected not only in infected-mid-aged mouse lungs but also in COVID-19-affected human autopsy lungs. This study suggests that the induction of ITGB3 expression in ECs is one of the mechanisms of thrombosis in severe COVID-19 pneumonia.
ISSN:2045-2322