| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Outline of Final Research Achievements |
Using a mouse model of hepatic ischemia/reperfusion injury (I/R injury), we explored the functional relevance of the VWF and ADAMTS13 molecules in this pathophysiologic condition. Time-course studies during hepatic I/R revealed significantly lower ALT values and greater hepatic blood flowin VWF knock-out mice (VWF-KO) mice than wild type mice (WT). Histological analysis revealed a significantly lesser extent of neutrophil infiltration of VWF-KO. Human recombinant ADAMTS13 significantly improved the I/R injury in WT similar level to VWF-KO. Real-time intravital imaging successfully visualized significantly reduced the number of leukocyte adhering to the vessel wall in VWF-KO mice. Taken together, our results indicate that VWF promotes microthrombosis and neutrophil recruitment and in ischemic 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.
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