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2020 Fiscal Year Final Research Report

Scientific Research for the Development of Novel Therapeutics in Marfan Syndrome Targeting Endothelial Cells-derived Oxidative Stress

Research Project

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Project/Area Number 18K08097
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53020:Cardiology-related
Research InstitutionThe University of Tokyo

Principal Investigator

Akazawa Hiroshi  東京大学, 医学部附属病院, 講師 (20396683)

Project Period (FY) 2018-04-01 – 2021-03-31
Keywords分子血管学
Outline of Final Research Achievements

We demonstrated that aberrant activation of mechanosensitive signaling in vascular endothelial cells triggered endothelial activation of xanthine oxidoreductase (XOR) and generation of reactive oxygen species (ROS), leading to progression of aneurysm formation in ascending aorta of Marfan syndrome.
There is currently no effective medical treatment, but our study highlights a drug repositioning approach using a uric acid lowering drug febuxostat as a potential therapy for Marfan syndrome.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

マルファン症候群はFBN1の遺伝子異常により全身の結合組織の構造・機能破綻を来す常染色体優性の希少難治性疾患である。MFSの遺伝子変異による疾患発症の分子機序はいまだに不明な点が多く残されていたが、本研究により血管内皮におけるxanthine oxidoreductase由来の酸化ストレスがマルファン症候群における大動脈瘤の病態形成に重要な役割を果たすことが明らかとなった。Xanthine oxidoreductase阻害薬であるfebuxostatの新規治療法開発へと応用されることが期待される。

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Published: 2022-01-27  

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