Molecular mechanism of cooperation between endothelial cell stiffness and functions.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08583
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Shimane University
• Principal Investigator: Okamoto Takayuki 島根大学, 学術研究院医学・看護学系, 准教授 (30378286)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 血管内皮細胞 / 細胞硬化 / 炎症 / 細胞骨格 / ギャップ結合

Outline of Final Research Achievements

In the current study, we analyzed the mechanisms by which endothelial cells increased cell stiffness upon inflammatory stimuli to regulate cellular functions. We found that cytoskeletal reorganization and activation of the transcriptional coactivator YAP, are implicated in cell stiffening upon inflammatory stimuli, lead to suppress Notch1 signaling. Our data also revealed that the expression of pro-inflammatory and angiogenesis related genes in endothelial cells is regulated under Notch1 signaling pathway. Furthermore, we showed that recombinant thrombomodulin protein, an anticoagulant and anti-inflammatory factor, attenuates leukocyte adhesion by inducing cell softening. In summary, our results indicate intracellular signaling and cellular functional changes associated with endothelial cell stiffening and suggest that this molecular pathway may be useful for the control of vascular inflammation.

Free Research Field

血管生物学

Academic Significance and Societal Importance of the Research Achievements

動脈血管の弾性増加（硬化）は、心血管イベント発症のリスクであり、また敗血症の予後不良に繋がる可能性が指摘されている。これは血管硬化が血栓形成や炎症の活性化を助長することを示唆し、我々は血管内皮細胞の硬化が炎症の増悪化を招く可能性を示してきた。本研究では細胞硬化を基軸として炎症拡大を引き起こす新しい分子機構を明らかにした点で学術的価値に優れる。また、本分子機構が動脈硬化や敗血症の基盤に存在する血管炎症を制御するための標的となる可能性を示し、これら疾患の新しい治療法への応用に繋がると考える。