Evidence map›Paper›PMID 26552708›Full record

ArticleThe Journal of experimental medicine2015

Endothelial NOTCH1 is suppressed by circulating lipids and antagonizes inflammation during atherosclerosis.

Anaïs Briot, Mete Civelek, Atsuko Seki, Karen Hoi, Julia J Mack, Stephen D Lee, Jason Kim, Cynthia Hong, Jingjing Yu, Gregory A Fishbein and 8 more

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

Article in The Journal of experimental medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
4.2field-weighted citation impact, top 5% 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

62 citing papers in PubMed, 106 citations in OpenAlex.

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  19. Article
  20. Notch Signaling in the Vasculature: Angiogenesis and Angiocrine Functions.Cold Spring Harbor perspectives in medicine · 2023
    Review

2 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

18 authors at 2 institutions in 1 country.

Anaïs BriotDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095.
Mete CivelekDepartment of Medicine, University of California, Los Angeles, Los Angeles, CA 90095.
Atsuko SekiDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095.
Karen HoiDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095.
Julia J MackDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095.
Stephen D LeeDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095 Howard Hughes Medical Institute, Los Angeles, CA 90095.
Jason KimDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095 Howard Hughes Medical Institute, Los Angeles, CA 90095.
Cynthia HongDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095 Howard Hughes Medical Institute, Los Angeles, CA 90095.
Jingjing YuDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095.
Gregory A FishbeinDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095.
Ladan VakiliDepartment of Medicine, University of California, Los Angeles, Los Angeles, CA 90095.
Alan M FogelmanDepartment of Medicine, University of California, Los Angeles, Los Angeles, CA 90095.
Michael C FishbeinDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095.
Aldons J LusisDepartment of Medicine, University of California, Los Angeles, Los Angeles, CA 90095.
Peter TontonozDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095 Howard Hughes Medical Institute, Los Angeles, CA 90095.
Mohamad NavabDepartment of Medicine, University of California, Los Angeles, Los Angeles, CA 90095.
Judith A BerlinerDepartment of Medicine, University of California, Los Angeles, Los Angeles, CA 90095 Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095.
M Luisa Iruela-ArispeDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095 Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095 arispe@mcdb.ucla.edu.
University of California, Los Angeles · USHoward Hughes Medical Institute · 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
Systems genomics of metabolic syndrome traitsP01HL028481 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PAJUKANTA, PAIVI · 1985 to 2019
$50.2M
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
Notch Signaling in Vascular Development and HomeostasisR01HL085618 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI IRUELA-ARISPE, M. LUISA · 2007 to 2011
$1.9M
Systems genetics analysis of cardiometabolic trait loci in humans R00HL121172 · NHLBI · UNIVERSITY OF VIRGINIA · PI CIVELEK, METE · 2016 to 2018
$741k
Systems genetics analysis of cardiometabolic trait loci in humans K99HL121172 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CIVELEK, METE · 2014 to 2015
$247k
Canadian Institutes of Health ResearchNHLBI NIH HHS HL28481NHLBI NIH HHS HL30568NHLBI NIH HHS K99 HL121172NHLBI NIH HHS K99HL121172NHLBI NIH HHS P01 HL028481NHLBI NIH HHS P01 HL030568NHLBI NIH HHS R00 HL121172NHLBI NIH HHS R01 HL085618NHLBI NIH HHS R01 HL114086NHLBI NIH HHS T32 HL069766NHLBI NIH HHS T32HL69766NIDDK NIH HHS P30 DK041301
6 · The paper itself

Abstract

Although much progress has been made in identifying the mechanisms that trigger endothelial activation and inflammatory cell recruitment during atherosclerosis, less is known about the intrinsic pathways that counteract these events. Here we identified NOTCH1 as an antagonist of endothelial cell (EC) activation. NOTCH1 was constitutively expressed by adult arterial endothelium, but levels were significantly reduced by high-fat diet. Furthermore, treatment of human aortic ECs (HAECs) with inflammatory lipids (oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine [Ox-PAPC]) and proinflammatory cytokines (TNF and IL1β) decreased Notch1 expression and signaling in vitro through a mechanism that requires STAT3 activation. Reduction of NOTCH1 in HAECs by siRNA, in the absence of inflammatory lipids or cytokines, increased inflammatory molecules and binding of monocytes. Conversely, some of the effects mediated by Ox-PAPC were reversed by increased NOTCH1 signaling, suggesting a link between lipid-mediated inflammation and Notch1. Interestingly, reduction of NOTCH1 by Ox-PAPC in HAECs was associated with a genetic variant previously correlated to high-density lipoprotein in a human genome-wide association study. Finally, endothelial Notch1 heterozygous mice showed higher diet-induced atherosclerosis. Based on these findings, we propose that reduction of endothelial NOTCH1 is a predisposing factor in the onset of vascular inflammation and initiation of atherosclerosis.

Indexed as

AdultAnimalsAtherosclerosisCell Line, TumorCells, CulturedDiet, High-FatEndothelial CellsFemaleHumansInflammationInterleukin-1betaLipidsMaleMice, Inbred C57BLMice, KnockoutMice, TransgenicInterleukin-1betaLipidsoxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholinePhosphatidylcholinesReceptor, Notch1Tumor Necrosis Factor-alpha

Identifiers

PMID26552708
PMCPMC4647265
OpenAlexW2176735297

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

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.