Blood-flow-mediated mechanotransduction in vascular endothelial cells

内皮细胞（ECs）感知剪切应力并将血流信息转化为功能反应，在血管稳态和病理生理中发挥重要作用。剪切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，但其机制尚不清楚。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离子通道引起的细胞外Ca2+内流。为了分析ArP释放的动力学，我们将细胞表面的ArP可视化。当受到剪切应力时，ECs在小泡处同时释放ArP。在ArP释放后，Ca2+波立即出现在ArP释放的同一部位。在剪切应力的作用下，整个EC膜的腔泡膜流动性增加。这些发现表明，atec膜直接响应剪切应力，这些变化与剪切-应力-机械传导机制有关。

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.