دورية أكاديمية
أعرض في EDS

NOTCH1 is a mechanosensor in adult arteries.

التفاصيل البيبلوغرافية
العنوان: NOTCH1 is a mechanosensor in adult arteries.
المؤلفون: 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.; Department of Ob-Gyn, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.; Molecular Biology Institute, University of California, Los Angeles, CA, 90095, USA., Zovein AC; Cardiovascular Research Institute, University of California, San Francisco, CA, 94158, USA., Fang Y; Department of Medicine, University of Chicago, Chicago, IL, 60637, USA., Tarling EJ; Department of Biological Chemistry, University of California, Los Angeles, CA, 90095, USA.; Molecular Biology Institute, University of California, Los Angeles, CA, 90095, USA.; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA., de Aguiar Vallim TQ; Department of Biological Chemistry, University of California, Los Angeles, CA, 90095, USA.; Molecular Biology Institute, University of California, Los Angeles, CA, 90095, USA.; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA., Navab M; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA., Fogelman AM; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA., Bouchard LS; Department of Bioengineering, University of California, Los Angeles, CA, 90095, USA.; Molecular Biology Institute, University of California, Los Angeles, CA, 90095, USA.; Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, 90095, USA., Iruela-Arispe ML; Department of Molecular, Cell & Developmental Biology, University of California, Los Angeles, CA, 90095, USA. arispe@mcdb.ucla.edu.; Molecular Biology Institute, University of California, Los Angeles, CA, 90095, USA. arispe@mcdb.ucla.edu.
المصدر: Nature communications [Nat Commun] 2017 Nov 20; Vol. 8 (1), pp. 1620. Date of Electronic Publication: 2017 Nov 20.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Mechanotransduction, Cellular*, Arteries/*metabolism , Receptor, Notch1/*metabolism, Animals ; Arteries/chemistry ; Calcium/metabolism ; Endothelial Cells/chemistry ; Endothelial Cells/metabolism ; Endothelium, Vascular/chemistry ; Endothelium, Vascular/metabolism ; Female ; Humans ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Receptor, Notch1/genetics ; Stress, Mechanical
مستخلص: 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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معلومات مُعتمدة: R01 HL114086 United States HL NHLBI NIH HHS; R00 HL103789 United States HL NHLBI NIH HHS; P30 DK041301 United States DK NIDDK NIH HHS; R01 HL130290 United States HL NHLBI NIH HHS; P01 HL030568 United States HL NHLBI NIH HHS; T32 HL069766 United States HL NHLBI NIH HHS; R01 HL136765 United States HL NHLBI NIH HHS
المشرفين على المادة: 0 (NOTCH1 protein, human)
0 (Notch1 protein, mouse)
0 (Receptor, Notch1)
SY7Q814VUP (Calcium)
تواريخ الأحداث: Date Created: 20171122 Date Completed: 20180914 Latest Revision: 20240216
رمز التحديث: 20240216
مُعرف محوري في PubMed: PMC5696341
DOI: 10.1038/s41467-017-01741-8
PMID: 29158473
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-017-01741-8