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Although there is evidence of the infection of ECs in human autopsy tissues, their detailed pathophysiology remains unclear due to the lack of animal model to study it. We used a mouse\u2010adapted SARS\u2010CoV\u20102 virus strain in young and mid\u2010aged mice. Only mid\u2010aged mice developed fatal pneumonia with thrombosis. Pulmonary ECs were isolated from these infected mice and RNA\u2010Seq was performed. The pulmonary EC transcriptome revealed that significantly higher levels of viral genes were detected in ECs from mid\u2010aged mice with upregulation of viral response genes such as DDX58 and IRF7. In addition, the thrombogenesis\u2010related genes encoding PLAT, PF4, F3 PAI\u20101, and P\u2010selectin were upregulated. In addition, the inflammation\u2010related molecules such as CXCL2 and CXCL10 were upregulated in the mid\u2010aged ECs upon viral infection. Our mouse model demonstrated that SARS\u2010CoV\u20102 virus entry into aged vascular ECs upregulated thrombogenesis and inflammation\u2010related genes and led to fatal pneumonia with thrombosis. Current results of EC transcriptome showed that EC uptake virus and become thrombogenic by activating neutrophils and platelets in the aged mice, suggesting age\u2010associated EC response as a novel finding in human severe COVID\u201019.<\/jats:p>","DOI":"10.1111\/acel.14050","type":"journal-article","created":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T06:23:06Z","timestamp":1702621386000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Viral uptake and pathophysiology of the lung endothelial cells in age\u2010associated severe <scp>SARS\u2010CoV<\/scp>\u20102 infection models"],"prefix":"10.1111","volume":"23","author":[{"given":"Takuya","family":"Tsumita","sequence":"first","affiliation":[{"name":"Department of Vascular Biology and Molecular Pathology, Faculty and Graduate School of Dental Medicine Hokkaido University  Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryo","family":"Takeda","sequence":"additional","affiliation":[{"name":"Department of Vascular Biology and Molecular Pathology, Faculty and Graduate School of Dental Medicine Hokkaido University  Sapporo Japan"},{"name":"Department of Oral Diagnosis and Medicine, Faculty and Graduate School of Dental Medicine Hokkaido University  Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nako","family":"Maishi","sequence":"additional","affiliation":[{"name":"Department of Vascular Biology and Molecular Pathology, Faculty and Graduate School of Dental Medicine Hokkaido University  Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiro","family":"Hida","sequence":"additional","affiliation":[{"name":"Department of Advanced Robotic and Endoscopic Surgery Fujita Health University  Toyoake Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michihito","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Division of Molecular Pathobiology, International Institute for Zoonosis Control Hokkaido University  Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuko","family":"Orba","sequence":"additional","affiliation":[{"name":"Division of Molecular Pathobiology, International Institute for Zoonosis Control Hokkaido University  Sapporo Japan"},{"name":"International Collaboration Unit, International Institute for Zoonosis Control Hokkaido University  Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihiko","family":"Sato","sequence":"additional","affiliation":[{"name":"Division of Molecular Pathobiology, International Institute for Zoonosis Control Hokkaido University  Sapporo Japan"},{"name":"Drug Discovery and Disease Research Laboratory Shionogi and Co., Ltd.  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