Von Willebrand Factor Aggravates Hepatic Ischemia-Reperfusion Injury by Promoting Neutrophil Recruitment in Mice.

• Material Type: 博士論文
• Title: Von Willebrand Factor Aggravates Hepatic Ischemia-Reperfusion Injury by Promoting Neutrophil Recruitment in Mice.
• Author/Editor: Urisono, Yasuyuki; Sakata, Asuka; Matsui, Hideto; Kasuda, Shogo; Ono, Shiro; Yoshimoto, Kiyomi; Nishio, Kenji; Sho, Masayuki; Akiyama, Masashi; Miyata, Toshiyuki; Okuchi, Kazuo; Nishimura, Satoshi; Sugimoto, Mitsuhiko
• Author Heading: Urisono, Yasuyuki; Sakata, Asuka; Matsui, Hideto; Kasuda, Shogo; Ono, Shiro; Yoshimoto, Kiyomi; Nishio, Kenji; Sho, Masayuki; Akiyama, Masashi; Miyata, Toshiyuki; Okuchi, Kazuo; Nishimura, Satoshi; Sugimoto, Mitsuhiko
• Publication, Distribution, etc.: Thieme
• Publication Date: 2018-04
• Publication Date (W3CDTF): 2018-04
• Alternative Title: Von Willebrand因子は、好中球の動員を促進してマウスの肝虚血再灌流障害を増悪させる
• Periodical title: Thrombosis and haemostasis
• No. or year of volume/issue: 118 4
• Volume: 118
• Issue: 4
• Pages: 700-708
• ISSN (Periodical Title): ISSN : 0340-6245
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2018-09-26
• Dissertation Number: 乙第1421号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: von Willebrand factor; ADAMTS13; hepatic ischaemia; reperfusion injury; neutrophil recruitment
• Target Audience: 一般
• Note (General): type:Thesis; Hepatic ischaemia-reperfusion (I/R) injury is a serious liver damage that critically influences the clinical outcome of liver surgery or transplantation. Since recent studies indicated the critical involvement of von Willebrand factor (VWF) in reperfusion injuries of brain and myocardium, we hypothesized that VWF-dependent thrombotic or inflammatory responses also play a role in hepatic I/R injury. Using a mouse model of hepatic I/R injury, we explored the functional relevance of the VWF-ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) axis in this pathologic condition. Time-course studies during hepatic I/R revealed significantly lower alanine aminotransferase (ALT) values, as well as greater hepatic blood flow, in VWF gene-deleted (KO) mice in comparison with wild-type (WT) mice. Histological analysis revealed a significantly lesser extent of neutrophil infiltration and hepatocellular necrosis in liver tissues of VWF-KO mice. Human recombinant ADAMTS13 significantly improved the impairment in ALT values and hepatic blood flow and decreased neutrophil infiltration within the liver tissue of WT mice. Real-time intravital imaging successfully visualized significantly reduced leukocyte-vessel wall interactions in I/R liver of VWF-KO mice. Taken together, our results indicate that VWF promotes neutrophil recruitment in ischaemic mouse liver, critically aggravating reperfusion injury, and suggest that functional regulation of VWF by ADAMTS13 represents a promising therapeutic option for hepatic I/R injury.; 博士（医学）・乙第1421号・平成30年9月26日; Copyright © 2018 Schattauer; © 2018. Thieme. All rights reserved.; This is a non-final version of an article published in final form in "http://dx.doi.org/10.1055/s-0038-1636529"; identifier:Thrombosis and haemostasis Vol.118 No.4 p.700-708 (2018 Apr); identifier:03406245; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3500; identifier:Thrombosis and haemostasis, 118(4): 700-708
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1055/s-0038-1636529
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU

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http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3500/1/01%e4%b9%991421%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3500/2/02%e4%b9%991421%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3500/6/03%e4%b9%991421%e6%9c%ac%e6%96%87.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3500/7/04%e4%b9%991421Figure01-05.pdf fulltext