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Critical role of oxidized LDL receptor-1 in intravascular thrombosis in a severe influenza mouse model

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Title: Critical role of oxidized LDL receptor-1 in intravascular thrombosis in a severe influenza mouse model
Authors: Ohno, Marumi Browse this author →KAKEN DB
Kakino, Akemi Browse this author
Sekiya, Toshiki Browse this author
Nomura, Naoki Browse this author
Shingai, Masashi Browse this author →KAKEN DB
Sawamura, Tatsuya Browse this author
Kida, Hiroshi Browse this author →KAKEN DB
Issue Date: 3-Aug-2021
Publisher: Nature Portfolio
Journal Title: Scientific reports
Volume: 11
Issue: 1
Start Page: 15675
Publisher DOI: 10.1038/s41598-021-95046-y
Abstract: Although coagulation abnormalities, including microvascular thrombosis, are thought to contribute to tissue injury and single- or multiple-organ dysfunction in severe influenza, the detailed mechanisms have yet been clarified. This study evaluated influenza-associated abnormal blood coagulation utilizing a severe influenza mouse model. After infecting C57BL/6 male mice with intranasal applications of 500 plaque-forming units of influenza virus A/Puerto Rico/8/34 (H1N1; PR8), an elevated serum level of prothrombin fragment 1+2, an indicator for activated thrombin generation, was observed. Also, an increased gene expression of oxidized low-density lipoprotein (LDL) receptor-1 (Olr1), a key molecule in endothelial dysfunction in the progression of atherosclerosis, was detected in the aorta of infected mice. Body weight decrease, serum levels of cytokines and chemokines, viral load, and inflammation in the lungs of infected animals were similar between wild-type and Olr1 knockout (KO) mice. In contrast, the elevation of prothrombin fragment 1+2 levels in the sera and intravascular thrombosis in the lungs by PR8 virus infection were not induced in KO mice. Collectively, the results indicated that OLR1 is a critical host factor in intravascular thrombosis as a pathogeny of severe influenza. Thus, OLR1 is a promising novel therapeutic target for thrombosis during severe influenza.
Type: article
Appears in Collections:人獣共通感染症国際共同研究所 (International Institute for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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