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NOTCH1 is a mechanosensor in adult arteries

Author

Listed:
  • 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
    University of California
    University of California)

  • Ann C. Zovein

    (University of California)

  • Yun Fang

    (University of Chicago)

  • Elizabeth J. Tarling

    (University of California
    University of California
    University of California)

  • Thomas Q. de Aguiar Vallim

    (University of California
    University of California
    University of California)

  • Mohamad Navab

    (University of California)

  • Alan M. Fogelman

    (University of California)

  • Louis S. Bouchard

    (University of California
    University of California
    University of California)

  • M. Luisa Iruela-Arispe

    (University of California
    University of California)

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.

Suggested Citation

  • 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-, 2017. "NOTCH1 is a mechanosensor in adult arteries," Nature Communications, Nature, vol. 8(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01741-8
    DOI: 10.1038/s41467-017-01741-8
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    Cited by:

    1. Jonas Stewen & Kai Kruse & Anca T. Godoi-Filip & Zenia & Hyun-Woo Jeong & Susanne Adams & Frank Berkenfeld & Martin Stehling & Kristy Red-Horse & Ralf H. Adams & Mara E. Pitulescu, 2024. "Eph-ephrin signaling couples endothelial cell sorting and arterial specification," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    2. Susanne Fleig & Tamar Kapanadze & Jeremiah Bernier-Latmani & Julia K. Lill & Tania Wyss & Jaba Gamrekelashvili & Dustin Kijas & Bin Liu & Anne M. Hüsing & Esther Bovay & Adan Chari Jirmo & Stephan Hal, 2022. "Loss of vascular endothelial notch signaling promotes spontaneous formation of tertiary lymphoid structures," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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