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NOTCH1 is a mechanosensor in adult arteries.
Mack, Julia J; Mosqueiro, Thiago S; Archer, Brian J; Jones, William M; Sunshine, Hannah; Faas, Guido C; Briot, Anais; Aragón, Raquel L; Su, Trent; Romay, Milagros C; McDonald, Austin I; Kuo, Cheng-Hsiang; Lizama, Carlos O; Lane, Timothy F; Zovein, Ann C; Fang, Yun; Tarling, Elizabeth J; de Aguiar Vallim, Thomas Q; Navab, Mohamad; Fogelman, Alan M; Bouchard, Louis S; Iruela-Arispe, M Luisa.
Afiliação
  • Mack JJ; Department of Molecular, Cell & Developmental Biology, University of California, Los Angeles, CA, 90095, USA.
  • Mosqueiro TS; Institute for Quantitative and Computational Biology, University of California, Los Angeles, CA, 90095, USA.
  • Archer BJ; Department of Bioengineering, University of California, Los Angeles, CA, 90095, USA.
  • Jones WM; Department of Molecular, Cell & Developmental Biology, University of California, Los Angeles, CA, 90095, USA.
  • Sunshine H; Interdepartmental Graduate Program in Molecular, Cellular and Integrative Physiology, University of California, Los Angeles, CA, 90095, USA.
  • Faas GC; Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
  • Briot A; Department of Molecular, Cell & Developmental Biology, University of California, Los Angeles, CA, 90095, USA.
  • Aragón RL; Molecular Biology Interdisciplinary Graduate Program, Molecular Biology Institute, University of California, Los Angeles, CA, 90095, USA.
  • Su T; Department of Biological Chemistry, University of California, Los Angeles, CA, 90095, USA.
  • Romay MC; Department of Molecular, Cell & Developmental Biology, University of California, Los Angeles, CA, 90095, USA.
  • McDonald AI; Molecular Biology Interdisciplinary Graduate Program, Molecular Biology Institute, University of California, Los Angeles, CA, 90095, USA.
  • Kuo CH; Department of Medicine, University of Chicago, Chicago, IL, 60637, USA.
  • Lizama CO; Cardiovascular Research Institute, University of California, San Francisco, CA, 94158, USA.
  • Lane TF; Department of Biological Chemistry, University of California, Los Angeles, CA, 90095, USA.
  • Zovein AC; Department of Ob-Gyn, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
  • Fang Y; Molecular Biology Institute, University of California, Los Angeles, CA, 90095, USA.
  • Tarling EJ; Cardiovascular Research Institute, University of California, San Francisco, CA, 94158, USA.
  • de Aguiar Vallim TQ; Department of Medicine, University of Chicago, Chicago, IL, 60637, USA.
  • Navab M; Department of Biological Chemistry, University of California, Los Angeles, CA, 90095, USA.
  • Fogelman AM; Molecular Biology Institute, University of California, Los Angeles, CA, 90095, USA.
  • Bouchard LS; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
  • Iruela-Arispe ML; Department of Biological Chemistry, University of California, Los Angeles, CA, 90095, USA.
Nat Commun ; 8(1): 1620, 2017 11 20.
Article em En | MEDLINE | ID: mdl-29158473
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Artérias / Mecanotransdução Celular / Receptor Notch1 Limite: Animals / Female / Humans / Male Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Adicionar na Minha BVS
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Artérias / Mecanotransdução Celular / Receptor Notch1 Limite: Animals / Female / Humans / Male Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Estados Unidos