Analyzing the shear‐induced sensitization of mechanosensitive ion channel Piezo‐1 in human aortic endothelial cells,Journal of Cellular Physiology

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Analyzing the shear‐induced sensitization of mechanosensitive ion channel Piezo‐1 in human aortic endothelial cells
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2020-09-22 , DOI: 10.1002/jcp.30056
Austin Lai ₁ , Yung C Chen _{1,

2} , Charles D Cox ₃ , Anthony Jaworowski ₁ , Karlheinz Peter _{1,

2} , Sara Baratchi _{1,

2}

Affiliation

Mechanosensitive ion channels mediate endothelial responses to blood flow and orchestrate their physiological function in response to hemodynamic forces. In this study, we utilized microfluidic technologies to study the shear‐induced sensitization of endothelial Piezo‐1 to its selective agonist, Yoda‐1. We demonstrated that shear stress‐induced sensitization is brief and can be impaired when exposing aortic endothelial cells to low and proatherogenic levels of shear stress. Our results suggest that shear stress‐induced sensitization of Piezo‐1 to Yoda‐1 is independent of cell–cell adhesion and is mediated by the PI3K‐AKT signaling pathway. We also found that shear stress increases the membrane density of Piezo‐1 channels in endothelial cells. To further confirm our findings, we performed experiments using a carotid artery ligation mouse model and demonstrated that transient changes in blood‐flow pattern, resulting from a high‐degree ligation of the mouse carotid artery alters the distribution of Piezo‐1 channels across the endothelial layer. These results suggest that shear stress influences the function of Piezo‐1 channels via changes in membrane density, providing a new model of shear‐stress sensitivity for Piezo‐1 ion channel.

中文翻译：

分析人主动脉内皮细胞中机械敏感离子通道 Piezo-1 的剪切致敏

机械敏感离子通道介导内皮对血流的反应，并协调它们对血流动力学的生理功能。在这项研究中，我们利用微流体技术来研究内皮 Piezo-1 对其选择性激动剂 Yoda-1 的剪切诱导敏感性。我们证明了剪切应力诱导的致敏作用是短暂的，当将主动脉内皮细胞暴露于低水平和促动脉粥样硬化水平的剪切应力时，可能会受到损害。我们的结果表明，剪切应力诱导的 Piezo-1 对 Yoda-1 的敏化与细胞间粘附无关，并由 PI3K-AKT 信号通路介导。我们还发现剪切应力增加了内皮细胞中 Piezo-1 通道的膜密度。为了进一步证实我们的发现，我们使用颈动脉结扎小鼠模型进行了实验，并证明了由小鼠颈动脉高度结扎引起的血流模式的瞬时变化改变了 Piezo-1 通道在内皮层的分布。这些结果表明，剪切应力通过膜密度的变化影响 Piezo-1 通道的功能，为 Piezo-1 离子通道提供了一种新的剪切应力敏感性模型。

更新日期：2020-09-22

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