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Elucidation of the significance of LOX-1 and endothelial dysfunction as the pathological basis of disseminated intravascular coagulation.

Research Project

Project/Area Number 18H02578
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 47040:Pharmacology-related
Research InstitutionShinshu University

Principal Investigator

Sawamura Tatsuya  信州大学, 学術研究院医学系, 教授 (30243033)

Co-Investigator(Kenkyū-buntansha) 垣野 明美  信州大学, 学術研究院医学系, 助教 (00534637)
藤田 佳子  信州大学, 医学部, 特任講師 (30416218)
堀内 清香  信州大学, 医学部, 特任助教 (20789820)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2021: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
KeywordsDIC / LOX-1 / 凝固因子
Outline of Final Research Achievements

To elucidate the pathophysiology of disseminated intravascular coagulation (DIC), it is necessary to know the coagulation promoting mechanism that works specifically in DIC. In this study, we elucidated the mechanism of coagulation promotion by LOX-1, and thrombomodulin, which is used as a therapeutic agent for DIC, and LOX-1 are controlled in opposition to each other in an animal model of DIC, suggesting the procoagulation-anticoagulation balance is regulated by these molecules. Furthermore, using tissue-specific LOX-1KO mice and LOX-1KO rats, we demonstrated that LOX-1 is involved in the pathology of DIC in animal models.

Academic Significance and Societal Importance of the Research Achievements

播種性血管内凝固症候群(DIC)は、未だ充分な治療法がなく致死率も高い病態である。それには、DICの病態が充分に解明されていないことが原因としてある。また、DICでは全身性に凝固系が亢進するが、一方で出血傾向も生じるため、単純に抗凝固薬によりコントロールするという戦略が取りにくい。そのため、DICに特有の凝固促進メカニズムを理解し、それを標的とすることが治療法開発には重要である。本研究では、まさにそのような病態生理上の位置で機能するメカニズムを見出し、実際にいくつかの動物モデルでその意義を検証することができた。これにより、未だ充分な治療法がなく致死率も高いDICの治療法への展開が期待される。

Report

(1 results)
  • 2021 Final Research Report ( PDF )

URL: 

Published: 2018-04-23   Modified: 2023-01-30  

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