2023 Fiscal Year Final Research Report
Mitochondria-mediated blood flow mechanosensing in endothelial cells
| Project/Area Number |
21H03791
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 90110:Biomedical engineering-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Yamamoto Kimiko 東京大学, 大学院医学系研究科(医学部), 准教授 (00323618)
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| Co-Investigator(Kenkyū-buntansha) |
安藤 譲二 獨協医科大学, 医学部, 特任教授 (20159528)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 血管内皮細胞 / せん断応力 / ミトコンドリア / ATP / メカノバイオロジー |
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| Outline of Final Research Achievements |
Endothelial cells (ECs) differentially sense laminar and disturbed flows by altering the lipid order of their plasma and mitochondrial membranes in opposite directions. This results in changes in mitochondrial function, namely, increased adenosine triphosphate (ATP) production for laminar flow and increased hydrogen peroxide (H2O2) release for disturbed flow, respectively. When cultured human aortic ECs were subjected to laminar or disturbed flow in flow-loading devices, the lipid order of their plasma membranes decreased in response to laminar flow and increased in response to disturbed flow. Laminar flow also decreased the lipid order of mitochondrial membranes and increased mitochondrial ATP production. In contrast, disturbed flow increased the lipid order of mitochondrial membranes and increased the release of H2O2 from the mitochondria. These results indicate that EC plasma membranes act as mechanosensors to shear stress and trigger changes in mitochondrial function.
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| Free Research Field |
生体医工学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、血管内皮細胞が血流をどのように感知し、細胞内に情報伝達するかを解明することを目的に、メカノセンサーとしての細胞形質膜とミトコンドリア機能とが密接に関連していることを始めて明らかにした。これまで、ミトコンドリアの活性がメカノセンシング機構に果たす役割を探る研究は殆ど例が無く、細胞内の微細構造とミトコンドリアATPと活性酸素シグナリングのリアルタイム解析を駆使して得られた結果は学術的に意義深い。また、メカノセンサーの本体が、層流が制御する血管系の恒常性維持と、乱流が惹起する血管病の発症の仕組みに果たす役割を解明したことは、血管病の予防や治療の基礎となる知見を与え、社会的意義がある。
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