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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/3500

Title: Von Willebrand Factor Aggravates Hepatic Ischemia-Reperfusion Injury by Promoting Neutrophil Recruitment in Mice.
Other Titles: 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
Authors: 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
Keywords: von Willebrand factor
ADAMTS13
hepatic ischaemia
reperfusion injury
neutrophil recruitment
Issue Date: Apr-2018
Publisher: Thieme
Citation: Thrombosis and haemostasis Vol.118 No.4 p.700-708 (2018 Apr)
Abstract: 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.
Description: 博士(医学)・乙第1421号・平成30年9月26日
Copyright © 2018 Schattauer
This is a non-final version of an article published in final form in "http://dx.doi.org/10.1055/s-0038-1636529"
URI: http://hdl.handle.net/10564/3500
ISSN: 03406245
Academic Degrees and number: 24601B1421
Degree-granting date: 2018-09-26
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2018年度

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