tetano
Editor, Senior Moderator
Sci Rep
. 2025 Jul 1;15(1):20447.
doi: 10.1038/s41598-025-02784-4. SARS-CoV-2 infection promotes lung thrombosis by inducing integrinβ3 expression in vascular endothelial cells
Wataru Ito[SUP] 1 2 [/SUP], Yuya Sakurai[SUP] 1 3 [/SUP], Nako Maishi[SUP] 1 [/SUP], Ryo Takeda[SUP] 1 4 [/SUP], Takahito Teshirogi[SUP] 1 3 [/SUP], Li Yu[SUP] 1 [/SUP], Yasuhiro Hida[SUP] 5 6 [/SUP], Michihito Sasaki[SUP] 7 8 [/SUP], Yasuko Orba[SUP] 7 9 10 8 [/SUP], Takuya Tsumita[SUP] 1 [/SUP], Haruhisa Watanabe[SUP] 11 [/SUP], Tadahiro Iimura[SUP] 11 [/SUP], Terufumi Kubo[SUP] 12 [/SUP], Shinsuke Toba[SUP] 7 13 [/SUP], Akihiko Sato[SUP] 7 13 8 [/SUP], Aya Matsuda[SUP] 1 [/SUP], Daisuke Kyuno[SUP] 12 [/SUP], Makoto Osanai[SUP] 12 [/SUP], Yoichi Ohiro[SUP] 2 [/SUP], Toshihiko Torigoe[SUP] 12 [/SUP], Hirofumi Sawa[SUP] 9 10 8 [/SUP], Kyoko Hida[SUP] 14 15 [/SUP]
Affiliations
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.
Keywords: Endothelial cells; Integrinβ3; Platelets; SARS-CoV-2; Thrombosis.
. 2025 Jul 1;15(1):20447.
doi: 10.1038/s41598-025-02784-4. SARS-CoV-2 infection promotes lung thrombosis by inducing integrinβ3 expression in vascular endothelial cells
Wataru Ito[SUP] 1 2 [/SUP], Yuya Sakurai[SUP] 1 3 [/SUP], Nako Maishi[SUP] 1 [/SUP], Ryo Takeda[SUP] 1 4 [/SUP], Takahito Teshirogi[SUP] 1 3 [/SUP], Li Yu[SUP] 1 [/SUP], Yasuhiro Hida[SUP] 5 6 [/SUP], Michihito Sasaki[SUP] 7 8 [/SUP], Yasuko Orba[SUP] 7 9 10 8 [/SUP], Takuya Tsumita[SUP] 1 [/SUP], Haruhisa Watanabe[SUP] 11 [/SUP], Tadahiro Iimura[SUP] 11 [/SUP], Terufumi Kubo[SUP] 12 [/SUP], Shinsuke Toba[SUP] 7 13 [/SUP], Akihiko Sato[SUP] 7 13 8 [/SUP], Aya Matsuda[SUP] 1 [/SUP], Daisuke Kyuno[SUP] 12 [/SUP], Makoto Osanai[SUP] 12 [/SUP], Yoichi Ohiro[SUP] 2 [/SUP], Toshihiko Torigoe[SUP] 12 [/SUP], Hirofumi Sawa[SUP] 9 10 8 [/SUP], Kyoko Hida[SUP] 14 15 [/SUP]
Affiliations
- PMID: 40594111
- PMCID: PMC12216270
- DOI: 10.1038/s41598-025-02784-4
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.
Keywords: Endothelial cells; Integrinβ3; Platelets; SARS-CoV-2; Thrombosis.