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GPR68 Senses Flow and Is Essential for Vascular Physiology

Xu, Jie, Vessieres, Emilie, Mathur, Jayanti, Hammack, Scott, Nonomura, Keiko, Favre, Julie, Grimaud, Linda, Petrus, Matthew, Francisco, Allain, Li, Jingyuan, Lee, Van, Xiang, Fuli, Mainquist, James, Cahalan, Stuart, Orth, Anthony, Walker, John, Ma, Shang, Lukacs, Viktor, Bordone, Laura, Bandell, Michael, Laffitte, Bryan, Xu, Yan, Chien, Shu, Henrion, Daniel and Patapoutian, Ardem (2018) GPR68 Senses Flow and Is Essential for Vascular Physiology. Cell, 173 (3). pp. 762-775. ISSN 00928674


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.

Item Type: Article
Keywords: GPR68, flow, shear stress, endothelial cells, resistance vessels, blood pressure
Date Deposited: 03 May 2018 00:45
Last Modified: 03 May 2018 00:45


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