Blood-flow-mediated mechanotransduction in vascular endothelial cells

血管内皮细胞中血流介导的机械转导

• 批准号: 22300150
• 负责人: YAMAMOTO Kimiko
• 金额: $ 11.73万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22300150/
• 关键词: バイオメカニクス; shear stress; 血管内皮細胞; 細胞膜; カベオラ; ATP; 流れ剪断応力; イオンチャネル; カルシウム・シグナリング; プリノセプター

Endothelial cells(ECs)sense shear stress and transduce blood flow infbrmation into functionalresponses that play important roles in vascular homeostasis and pathophysiology. A unique feature ofshear-stress-sensing is the involvement of many different types of membrane-bound molecules, but themechanisms remain unknown. Shear stress evokes a rapid, dose-dependent increase in intracellular Ca2+concentration caused by an influx of extracellular Ca2+via ATP-operated P2×4 ion channels activatedby endogenous ArP released by ECs. To analyze the dynamics of ArP release, we visualized ArP at thecell surface. When exposed to shear stress, ECs simultaneously released ArP at caveolae. Immediatelyafter the ArP release, Ca2+wave occurred at the same site as the ArP release. Caveolar membranefluidity increased over the entire EC membranes in response to shear stress. These findings indicate thatEC membranes directly respond to shear stress and that these changes link to shear-stress-mechanotranuction mechnisms.

血管内皮细胞(ECs)感知切应力，将血流信息转化为功能反应，在血管内稳态和病理生理中发挥重要作用。剪应力传感的一个独特特征是涉及许多不同类型的膜结合分子，但机制尚不清楚。由内皮细胞释放的内源性ARP激活的ATP操作的P2×4离子通道引起细胞外钙离子内流，引起剪切力引起细胞内钙离子浓度的快速、剂量依赖性增加。为了分析ARP的释放动力学，我们在细胞表面可视化了ARP。当受到切应力时，内皮细胞同时在小窝释放ARP。ARP释放后即刻，钙波出现在与ARP释放相同的位置。腔泡膜流动性在整个EC膜上增加，以响应切应力。这些发现表明EC膜直接对切应力作出反应，并且这些变化与切应力-机械传导机制有关。

项目成果

Mechanosensing of blood flow in vascular endothelial cells

血管内皮细胞血流的机械传感

• DOI: 10.1254/fpj.138.196
• 发表时间: 2011
• 期刊: Folia Pharmacologica Japonica
• 作者: 山本希美子;安藤譲二
• 通讯作者: 安藤譲二

Shear-stress-mediated control of vascular functions through endothelial ATP release and P2X4 receptors

通过内皮 ATP 释放和 P2X4 受体剪切应力介导的血管功能控制

• 发表时间: 2011
• 作者: K.Yamamoto;J.Ando
• 通讯作者: J.Ando

Dynamic cellular mechanotransduction and nano-biomechanics

动态细胞力转导和纳米生物力学

• 发表时间: 2013
• 作者: Ishitobi H;Wakamatsu A;Lui F;Azami T;Hamada M;Matsumoto K;Kataoka H;kobayashi M;Choi K;Nishikawa S-I;Takahashi S;Ema M;K. Yamamoto and J. Ando
• 通讯作者: K. Yamamoto and J. Ando

Biomedical force-induced differentiation of ES cells into vascular cells

生物医学力诱导ES细胞分化为血管细胞

• 发表时间: 2010
• 作者: J.Ando;K.Yamamoto
• 通讯作者: K.Yamamoto

Molecular Mechanisms Underlying Mechanosensing in Vascular Biology in "Mechanosensing Biology"

“机械传感生物学”中血管生物学机械传感的分子机制

• 发表时间: 2011
• 作者: K.Yamamoto;J.Ando
• 通讯作者: J.Ando