NOTCH1 is a mechanosensor in adult arteries

Julia J. Mack, Thiago S. Mosqueiro, Brian J. Archer, William M. Jones, Hannah Sunshine, Guido C. Faas, Anais Briot, Raquel L. Aragón, Trent Su, Milagros C. Romay, Austin I. McDonald, Cheng-Hsiang Kuo, Carlos O. Lizama, Timothy F. Lane, Ann C. Zovein, Yun Fang, Elizabeth J. Tarling, Thomas Q. de Aguiar Vallim, Mohamad Navab, Alan M. Fogelman, Louis S. Bouchard and M. Luisa Iruela-Arispe ()
Additional contact information
Julia J. Mack: University of California
Thiago S. Mosqueiro: University of California
Brian J. Archer: University of California
William M. Jones: University of California
Hannah Sunshine: University of California
Guido C. Faas: University of California
Anais Briot: University of California
Raquel L. Aragón: University of California
Trent Su: University of California
Milagros C. Romay: University of California
Austin I. McDonald: University of California
Cheng-Hsiang Kuo: University of Chicago
Carlos O. Lizama: University of California
Timothy F. Lane: University of California
Ann C. Zovein: University of California
Yun Fang: University of Chicago
Elizabeth J. Tarling: University of California
Thomas Q. de Aguiar Vallim: University of California
Mohamad Navab: University of California
Alan M. Fogelman: University of California
Louis S. Bouchard: University of California
M. Luisa Iruela-Arispe: University of California

Nature Communications, 2017, vol. 8, issue 1, 1-19

Abstract: Abstract Endothelial cells transduce mechanical forces from blood flow into intracellular signals required for vascular homeostasis. Here we show that endothelial NOTCH1 is responsive to shear stress, and is necessary for the maintenance of junctional integrity, cell elongation, and suppression of proliferation, phenotypes induced by laminar shear stress. NOTCH1 receptor localizes downstream of flow and canonical NOTCH signaling scales with the magnitude of fluid shear stress. Reduction of NOTCH1 destabilizes cellular junctions and triggers endothelial proliferation. NOTCH1 suppression results in changes in expression of genes involved in the regulation of intracellular calcium and proliferation, and preventing the increase of calcium signaling rescues the cell–cell junctional defects. Furthermore, loss of Notch1 in adult endothelium increases hypercholesterolemia-induced atherosclerosis in the descending aorta. We propose that NOTCH1 is atheroprotective and acts as a mechanosensor in adult arteries, where it integrates responses to laminar shear stress and regulates junctional integrity through modulation of calcium signaling.

Date: 2017
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01741-8

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DOI: 10.1038/s41467-017-01741-8

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