2023 Fiscal Year Final Research Report

Elucidation of moyamoya disease pathophysiology through an interaction of hemodynamics and endothelial cells

Research Project

PDF

Project/Area Number	21H04835
Research Category	Grant-in-Aid for Scientific Research (A)
Allocation Type	Single-year Grants
Section	一般
Review Section	Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
Research Institution	Tohoku University
Principal Investigator	Tominaga Teiji 東北大学, 大学病院, 教授 (00217548)
Co-Investigator(Kenkyū-buntansha)	藤村幹北海道大学, 医学研究院, 教授 (00361098) Rashad Sherif 東北大学, 医工学研究科, 准教授 (00824088) 新妻邦泰東北大学, 医工学研究科, 教授 (10643330) 森戸大介昭和大学, 医学部, 講師 (20514251) 下田由輝東北大学, 大学病院, 助教 (30815444)
Project Period (FY)	2021-04-05 – 2024-03-31
Keywords	もやもや病 / RNF213 / 血流 / 内皮細胞 / 数値流体力学
Outline of Final Research Achievements	Moyamoya disease, discovered in Japan, is an idiopathic condition characterized by progressive stenosis and occlusion of the bilateral internal carotid arteries, along with the development of abnormal vascular networks. The aim of this study is to elucidate the mechanisms of onset and progression of moyamoya disease, which remain unknown, from the perspective of interactions between blood flow and vascular endothelium. We conducted elemental studies including computational fluid dynamics analysis, fluid culture analysis, immunological analysis, biomarker exploration, and analysis of RNF213 function. As a result, it was shown that the RNF213 gene changes in a shear stress-dependent manner due to blood flow, implicating it in inflammation through leukocyte adhesion and migration, suggesting that interactions between blood flow and vascular endothelium contribute to the pathology.
Free Research Field	脳神経外科学
Academic Significance and Societal Importance of the Research Achievements	未だ原因が不明、かつ若年者の脳卒中に関連するもやもや病の病態に、血流と血管壁の細胞の間の相互作用がかかわることを本研究で示しました。その結果として、様々な遺伝子産物や白血球の反応が変化することも示されました。また、血液中のデスモシンという物質が、もやもや病の進行に関係することなども示されました。本研究結果をさらに発展することで、もやもや病の新規治療薬の開発などにつながる可能性が示唆されました。