2022 Fiscal Year Final Research Report
Elucidation of the association between TMA and VOD, and development of novel therapy for VOD from a viewpoint of TMA treatment
| Project/Area Number |
18K16277
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Keywords | 肝類洞閉塞症候群 / 血栓性微小血管障害 / von Willebrand factor / ADAMTS13 / 血小板減少 / VOD / TMA |
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| Outline of Final Research Achievements |
Hepatic sinusoidal obstruction syndrome (VOD) and thrombotic microangiopathy (TMA), if advanced, develop organ dysfunction and poor prognosis. No studies have focused on the relationship between the two diseases. In this study, mouse model of VOD was used and evaluated for TMA pathogenesis; platelet aggregation along sinusoids and von Willebrand factor (vWF) aggregation were observed in the liver tissue of VOD. In plasma, ADAMTS13 activity decreased from the early stage of VOD, whereas vWF concentration continued to increase. This study confirmed TMA pathology in the liver tissue of VOD and suggested that the changes of ADAMTS13 activity and vWF concentration in plasma may be useful as biomarkers of VOD.
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| Free Research Field |
肝臓外科
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| Academic Significance and Societal Importance of the Research Achievements |
肝類洞閉塞症候群（VOD）および血栓性微小血管障害（TMA）は、ともに移植医療や化学療法（造血幹細胞移植の前処置、消化器悪性腫瘍に対して使用されるオキサリプラチンなど）における合併症や副作用として認められ、進行すると臓器不全に進展する予後不良な疾患である。本研究により、両疾患の病態には関連性があることが基礎実験により明らかになった。特に血漿中に認められたADAMTS13活性やvWF濃度の変化は、VODのバイオマーカーや早期治療介入の指標となると考えられた。今後、本研究結果がエビデンスとなり、両疾患に関連した研究が継続され、有効な治療法や予防対策の開発につながることが期待される。
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