並列タイトル等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
タイトル(掲載誌)Thrombosis and haemostasis
一般注記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
連携機関・データベース国立情報学研究所 : 学術機関リポジトリデータベース(IRDB)(機関リポジトリ)
提供元機関・データベース奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU