Evidence map›Paper›PMID 29158473›Full record

ArticleNature communications2017

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 and 12 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 202 papers.

0numbers the graph read from it
0cells of the map it votes in
202citing papers in PubMed
13.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

202 citing papers in PubMed, 301 citations in OpenAlex.

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  8. Skin capillary endothelial cells form a network of spatiotemporally conserved CaProceedings of the National Academy of Sciences of the United States of America · 2026
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142 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors at 4 institutions in 1 country.

Julia J MackDepartment of Molecular, Cell & Developmental Biology, University of California, Los Angeles, CA, 90095, USA.
Thiago S MosqueiroInstitute for Quantitative and Computational Biology, University of California, Los Angeles, CA, 90095, USA.
Brian J ArcherDepartment of Bioengineering, University of California, Los Angeles, CA, 90095, USA.
William M JonesDepartment of Molecular, Cell & Developmental Biology, University of California, Los Angeles, CA, 90095, USA.
Hannah SunshineInterdepartmental Graduate Program in Molecular, Cellular and Integrative Physiology, University of California, Los Angeles, CA, 90095, USA.
Guido C FaasDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Anais BriotDepartment of Molecular, Cell & Developmental Biology, University of California, Los Angeles, CA, 90095, USA.
Raquel L AragónMolecular Biology Interdisciplinary Graduate Program, Molecular Biology Institute, University of California, Los Angeles, CA, 90095, USA.
Trent SuDepartment of Biological Chemistry, University of California, Los Angeles, CA, 90095, USA.
Milagros C RomayDepartment of Molecular, Cell & Developmental Biology, University of California, Los Angeles, CA, 90095, USA.
Austin I McDonaldMolecular Biology Interdisciplinary Graduate Program, Molecular Biology Institute, University of California, Los Angeles, CA, 90095, USA.
Cheng-Hsiang KuoDepartment of Medicine, University of Chicago, Chicago, IL, 60637, USA.
Carlos O LizamaCardiovascular Research Institute, University of California, San Francisco, CA, 94158, USA.
Timothy F LaneDepartment of Biological Chemistry, University of California, Los Angeles, CA, 90095, USA.
Ann C ZoveinCardiovascular Research Institute, University of California, San Francisco, CA, 94158, USA.ORCID http://orcid.org/0000-0003-3298-7308
Yun FangDepartment of Medicine, University of Chicago, Chicago, IL, 60637, USA.
Elizabeth J TarlingDepartment of Biological Chemistry, University of California, Los Angeles, CA, 90095, USA.
Thomas Q de Aguiar VallimDepartment of Biological Chemistry, University of California, Los Angeles, CA, 90095, USA.
Mohamad NavabDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Alan M FogelmanDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Louis S BouchardDepartment of Bioengineering, University of California, Los Angeles, CA, 90095, USA.
M Luisa Iruela-ArispeDepartment of Molecular, Cell & Developmental Biology, University of California, Los Angeles, CA, 90095, USA. arispe@mcdb.ucla.edu.
University of California, Los Angeles · USUniversity of California, San Francisco · USUniversity of Chicago · USQB3 · US

Funding

ULTRASTRUCTURE OF THE INTIMA IN EARLY LESION FORMATIONP01HL030568 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FOGELMAN, ALAN M · 1985 to 2019
$55.2M
UCLA-Caltech Medical Scientist Training ProgramT32GM008042 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AJIJOLA, OLUJIMI A, DAWSON, DAVID WAYNE · 1985 to 2023
$29.9M
Pilot and Feasibility ProgramP30DK041301 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ROZENGURT, JUAN ENRIQUE · 1990 to 2019
$18.0M
Vascular Biology Training GrantT32HL069766 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LUSIS, ALDONS JAKE · 2002 to 2022
$7.4M
Induction of Vascular MorphogenesisR01HL114086 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BOUCHARD, LOUIS, IRUELA-ARISPE, M. LUISA · 2013 to 2016
$2.1M
Coronary artery disease locus 1p32.2 and miR92a-PPAP2B signaling in endothelial mechanobiologyR01HL136765 · NHLBI · UNIVERSITY OF CHICAGO · PI FANG, YUN · 2017 to 2021
$2.0M
Homeostasis in Adult VesselsR01HL130290 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI IRUELA-ARISPE, M. LUISA · 2016 to 2018
$892k
miR-10a regulation of regional arterial endothelial phenotypes in atherosclerosisR00HL103789 · NHLBI · UNIVERSITY OF CHICAGO · PI FANG, YUN · 2013 to 2015
$729k
NHLBI NIH HHS P01 HL030568NHLBI NIH HHS R00 HL103789NHLBI NIH HHS R01 HL114086NHLBI NIH HHS R01 HL130290NHLBI NIH HHS R01 HL136765NHLBI NIH HHS T32 HL069766NIDDK NIH HHS P30 DK041301
6 · The paper itself

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.

Indexed as

Mechanotransduction, CellularAnimalsArteriesCalciumEndothelial CellsEndothelium, VascularFemaleHumansMaleMice, Inbred C57BLMice, KnockoutReceptor, Notch1Stress, MechanicalCalciumNOTCH1 protein, humanNotch1 protein, mouseReceptor, Notch1

Identifiers

PMID29158473
PMCPMC5696341
OpenAlexW2768469522

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.