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. FogelmanLouis S. Bouchard, M. Luisa Iruela-Arispe

研究成果: Article

35 引文 (Scopus)

摘要

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.

原文English
文章編號1620
期刊Nature communications
8
發行號1
DOIs
出版狀態Published - 2017 十二月 1

指紋

arteries
shear stress
Shear stress
Calcium Signaling
Arteries
calcium
Calcium
integrity
cells
retarding
Hypercholesterolemia
endothelium
Thoracic Aorta
arteriosclerosis
homeostasis
aorta
phenotype
Endothelium
Blood Vessels
Atherosclerosis

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

引用此文

Mack, J. J., Mosqueiro, T. S., Archer, B. J., Jones, W. M., Sunshine, H., Faas, G. C., ... Iruela-Arispe, M. L. (2017). NOTCH1 is a mechanosensor in adult arteries. Nature communications, 8(1), [1620]. https://doi.org/10.1038/s41467-017-01741-8
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. / NOTCH1 is a mechanosensor in adult arteries. 於: Nature communications. 2017 ; 卷 8, 編號 1.
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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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Mack, JJ, Mosqueiro, TS, Archer, BJ, Jones, WM, Sunshine, H, Faas, GC, Briot, A, Aragón, RL, Su, T, Romay, MC, McDonald, AI, Kuo, CH, Lizama, CO, Lane, TF, Zovein, AC, Fang, Y, Tarling, EJ, De Aguiar Vallim, TQ, Navab, M, Fogelman, AM, Bouchard, LS & Iruela-Arispe, ML 2017, 'NOTCH1 is a mechanosensor in adult arteries', Nature communications, 卷 8, 編號 1, 1620. https://doi.org/10.1038/s41467-017-01741-8

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.

於: Nature communications, 卷 8, 編號 1, 1620, 01.12.2017.

研究成果: Article

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AU - Faas, Guido C.

AU - Briot, Anais

AU - Aragón, Raquel L.

AU - Su, Trent

AU - Romay, Milagros C.

AU - McDonald, Austin I.

AU - Kuo, Cheng Hsiang

AU - Lizama, Carlos O.

AU - Lane, Timothy F.

AU - Zovein, Ann C.

AU - Fang, Yun

AU - Tarling, Elizabeth J.

AU - De Aguiar Vallim, Thomas Q.

AU - Navab, Mohamad

AU - Fogelman, Alan M.

AU - Bouchard, Louis S.

AU - Iruela-Arispe, M. Luisa

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Mack JJ, Mosqueiro TS, Archer BJ, Jones WM, Sunshine H, Faas GC 等. NOTCH1 is a mechanosensor in adult arteries. Nature communications. 2017 12月 1;8(1). 1620. https://doi.org/10.1038/s41467-017-01741-8