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2020 Fiscal Year Final Research Report

Elucidation of biological defense mechanism by tyrosine kinase Syk in aortic dissection and therapeutic application

Research Project

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Project/Area Number 19K18197
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 55030:Cardiovascular surgery-related
Research InstitutionKurume University

Principal Investigator

Hashimoto Yohei  久留米大学, 医学部, 助教 (10811086)

Project Period (FY) 2019-04-01 – 2021-03-31
KeywordsSyk / 大動脈解離 / マクロファージ / 平滑筋 / spleen tyrosine kinase
Outline of Final Research Achievements

In pathogenesis of aortic dissection (AD), smooth muscle and inflammatory cells participate in tissue destruction and defense. We found that Syk was activated in inflammatory and smooth muscle cells in AD. Administration of fostamatinib, a specific Syk inhibitor, resulted in worsening of AD with increase in mortality. Analyses of transcriptome and inflammatory cytokines indicated that fostamatinib suppressed systemic inflammatory response, but augmented local inflammatory response with suppression of regulatory T cell in the aorta. Syk may coordinate the systemic and local inflammatory responses to protect aorta from AD.

Free Research Field

循環器

Academic Significance and Societal Importance of the Research Achievements

大動脈解離は中高年に好発する致死的な急性大動脈症候群の1つである。人口の高齢化に伴い増加しているが、発症機序や分子病態に謎が多く新たな診断・治療・予防法の開発の妨げとなっている。本研究の結果から、Syk阻害が解離の増悪と死亡率増加を助長することが明らかになった。Syk活性が大動脈解離病態において免疫関連分子を制御し大動脈組織保護の中心的役割を果たすことが示唆され、解離病態解明に繋がる新たな知見となった。また、偶発的ではあるが、Syk阻害薬が免疫寛容の主体である制御性T細胞を抑制していることも示唆し他分野への応用に繋がる知見を得た。

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Published: 2022-01-27  

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