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.

内皮细胞（EC）感知剪切应力并将血流信息转化为在血管稳态和病理生理学中发挥重要作用的功能反应，剪切应力感知的一个独特特征是许多不同类型的膜结合分子的参与。仍然未知 剪切应力引起细胞内 Ca2+ 浓度的快速、剂量依赖性增加，这是由细胞外 Ca2+ 流入引起的由 EC 释放的内源性 ArP 激活的 ATP 操作的 P2×4 离子通道 为了分析 ArP 释放的动态，我们观察了细胞表面的 ArP，当暴露于剪切应力时，EC 在 ArP 释放后立即在小凹处释放 ArP。波发生在与 ArP 释放相同的位置，整个 EC 膜的流动性随着剪切应力而增加。这些发现表明 EC 膜直接响应。剪切应力，这些变化与剪切应力机械传动机制有关。

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-sensing and response mechanisms in vascular endothelial cells. IN "Interface Oral Health Science 2009"

血管内皮细胞的剪切应力感应和响应机制。

• 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

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

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