Mechanotransduction plays a crucial role in vascular biology. One example of this is the local regulation of vascular resistance via flow-mediated dilation (FMD). Impairment of this process is a hallmark of endothelial dysfunction and a precursor to a wide array of vascular diseases, such as hypertension and atherosclerosis. Yet the molecules responsible for sensing flow (shear stress) within endothelial cells remain largely unknown. We designed a 384-well screening system that applies shear stress on cultured cells. We identified a mechanosensitive cell line that exhibits shear stress-activated calcium transients, screened a focused RNAi library, and identified GPR68 as necessary and sufficient for shear stress responses. GPR68 is expressed in endothelial cells of small-diameter (resistance) arteries. Importantly, Gpr68-deficient mice display markedly impaired acute FMD and chronic flow-mediated outward remodeling in mesenteric arterioles. Therefore, GPR68 is an essential flow sensor in arteriolar endothelium and is a critical signaling component in cardiovascular pathophysiology.

中文翻译：

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GPR68感应流量，对血管生理至关重要。

机械转导在血管生物学中起着至关重要的作用。这样的一个例子是通过流介导的扩张（FMD）对血管阻力的局部调节。该过程的损害是内皮功能障碍的标志，并且是多种血管疾病如高血压和动脉粥样硬化的先兆。然而，负责感知内皮细胞内流动（剪切应力）的分子仍是未知之数。我们设计了一个384孔筛选系统，将剪切应力施加到培养的细胞上。我们确定了一个机械敏感的细胞系，表现出剪切应力激活的钙瞬变，筛选了一个集中的RNAi文库，并确定GPR68是必要的和足够的剪切应力反应。GPR68在小直径（阻力）动脉的内皮细胞中表达。重要的，Gpr68缺陷小鼠在肠系膜小动脉中显示出明显的急性FMD受损和慢性血流介导的向外重塑。因此，GPR68是小动脉内皮中必不可少的流量传感器，并且是心血管病理生理中的关键信号组件。