A novel therapeutic approach to control vascular hyperpermiability using platelet-derived products.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09406
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55060:Emergency medicine-related
• Research Institution: Kurume University
• Principal Investigator: Takasu Osamu 久留米大学, 医学部, 教授 (90236216)
• Co-Investigator(Kenkyū-buntansha): 平湯 恒久 久留米大学, 医学部, 助教 (00647745) ; 鍋田 雅和 久留米大学, 医学部, 助教 (20529523)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 敗血症 / 血小板 / 血管透過性亢進 / 血小板由来蛋白 / 血小板由来細胞外小胞 / EVカドヘリン

Outline of Final Research Achievements

The effects of platelet endogenous proteins and extracellular vesicles (EVs) released with platelet activation during sepsis on the vascular endothelium are unknown. In this study, three fractions: Platelet derived endogenous proteins, Platelet derived large-EVs and small- EVs, were created and separated from washed platelets, and their effects were investigated.
The endogenous protein enhanced the junction of the injured vascular endothelium on cultured endothelium and reduced the vascular endothelial injury in the sepsis model. However, although the direct effect of EVs on the vascular endothelium could not be clarified, large-EVs capable of thrombin generation increased plasma Gasdermin D. On the other hand, administration of small EVs suppressed Gasdemin D production, thus controlling inflammation. It was suggested that small EVs have ability to suppress indirectly vascular injury.

Free Research Field

敗血症、臓器不全、救急集中治療

Academic Significance and Societal Importance of the Research Achievements

高齢化が進む本邦では、今後、敗血症患者数の増加が予測される。敗血症時には血小板の活性化に伴い、内在する様々な蛋白や細胞外小胞が放出され、これが敗血症の病態と深く関わっている事が知られている。血小板活性化が敗血症病態の進展悪化に繋がるという考えに立てば、高齢者で服用率が高い血小板凝集抑制薬は、敗血症の予後を変える可能性もある。
一方、本研究は、血小板の活性化で放出される物質を、血管内皮傷害に対して正の制御（傷害の進行防止や回復）を示す分画と傷害性を示す分画とに分離できれば、血小板のモジュレートのもと血管内皮傷害の制御や修復をターゲットとする新たな敗血症治療法が生まれる可能性を示したものと考える。