Evidence map›Paper›PMID 28674041›Full record

ArticleCirculation research2017

Transient Notch Activation Induces Long-Term Gene Expression Changes Leading to Sick Sinus Syndrome in Mice.

Yun Qiao, Catherine Lipovsky, Stephanie Hicks, Somya Bhatnagar, Gang Li, Aditi Khandekar, Robert Guzy, Kel Vin Woo, Colin G Nichols, Igor R Efimov and 1 more

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

Article in Circulation research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

22 citing papers in PubMed, 28 citations in OpenAlex.

  1. Trial
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  10. Methyltransferase SET domain family and its relationship with cardiovascular development and diseases.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2022
    Article
  11. Review
  12. Pharmacologic Approach to Sinoatrial Node Dysfunction.Annual review of pharmacology and toxicology · 2021
    Review
  13. GATA6 is a regulator of sinus node development and heart rhythm.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  14. Article
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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

11 authors at 1 institution in 1 country.

Yun QiaoFrom the Department of Medicine, Cardiovascular Division (Y.Q., C.L., S.H., S.B., G.L., A.K., S.R.), Department of Biomedical Engineering (Y.Q., G.L., S.R.), Department of Developmental Biology (C.L., S.B., S.R.), Department of Pediatrics (K.V.W.), and Department of Cell Biology (C.G.N.), Washington University in St Louis, MO; Department of Medicine, University of Chicago, IL (R.G.); and Department of Biomedical Engineering, The George Washington University, Science and Engineering Hall, Washington DC (Y.Q., I.R.E.).
Catherine LipovskyFrom the Department of Medicine, Cardiovascular Division (Y.Q., C.L., S.H., S.B., G.L., A.K., S.R.), Department of Biomedical Engineering (Y.Q., G.L., S.R.), Department of Developmental Biology (C.L., S.B., S.R.), Department of Pediatrics (K.V.W.), and Department of Cell Biology (C.G.N.), Washington University in St Louis, MO; Department of Medicine, University of Chicago, IL (R.G.); and Department of Biomedical Engineering, The George Washington University, Science and Engineering Hall, Washington DC (Y.Q., I.R.E.).
Stephanie HicksFrom the Department of Medicine, Cardiovascular Division (Y.Q., C.L., S.H., S.B., G.L., A.K., S.R.), Department of Biomedical Engineering (Y.Q., G.L., S.R.), Department of Developmental Biology (C.L., S.B., S.R.), Department of Pediatrics (K.V.W.), and Department of Cell Biology (C.G.N.), Washington University in St Louis, MO; Department of Medicine, University of Chicago, IL (R.G.); and Department of Biomedical Engineering, The George Washington University, Science and Engineering Hall, Washington DC (Y.Q., I.R.E.).
Somya BhatnagarFrom the Department of Medicine, Cardiovascular Division (Y.Q., C.L., S.H., S.B., G.L., A.K., S.R.), Department of Biomedical Engineering (Y.Q., G.L., S.R.), Department of Developmental Biology (C.L., S.B., S.R.), Department of Pediatrics (K.V.W.), and Department of Cell Biology (C.G.N.), Washington University in St Louis, MO; Department of Medicine, University of Chicago, IL (R.G.); and Department of Biomedical Engineering, The George Washington University, Science and Engineering Hall, Washington DC (Y.Q., I.R.E.).
Gang LiFrom the Department of Medicine, Cardiovascular Division (Y.Q., C.L., S.H., S.B., G.L., A.K., S.R.), Department of Biomedical Engineering (Y.Q., G.L., S.R.), Department of Developmental Biology (C.L., S.B., S.R.), Department of Pediatrics (K.V.W.), and Department of Cell Biology (C.G.N.), Washington University in St Louis, MO; Department of Medicine, University of Chicago, IL (R.G.); and Department of Biomedical Engineering, The George Washington University, Science and Engineering Hall, Washington DC (Y.Q., I.R.E.).
Aditi KhandekarFrom the Department of Medicine, Cardiovascular Division (Y.Q., C.L., S.H., S.B., G.L., A.K., S.R.), Department of Biomedical Engineering (Y.Q., G.L., S.R.), Department of Developmental Biology (C.L., S.B., S.R.), Department of Pediatrics (K.V.W.), and Department of Cell Biology (C.G.N.), Washington University in St Louis, MO; Department of Medicine, University of Chicago, IL (R.G.); and Department of Biomedical Engineering, The George Washington University, Science and Engineering Hall, Washington DC (Y.Q., I.R.E.).
Robert GuzyFrom the Department of Medicine, Cardiovascular Division (Y.Q., C.L., S.H., S.B., G.L., A.K., S.R.), Department of Biomedical Engineering (Y.Q., G.L., S.R.), Department of Developmental Biology (C.L., S.B., S.R.), Department of Pediatrics (K.V.W.), and Department of Cell Biology (C.G.N.), Washington University in St Louis, MO; Department of Medicine, University of Chicago, IL (R.G.); and Department of Biomedical Engineering, The George Washington University, Science and Engineering Hall, Washington DC (Y.Q., I.R.E.).
Kel Vin WooFrom the Department of Medicine, Cardiovascular Division (Y.Q., C.L., S.H., S.B., G.L., A.K., S.R.), Department of Biomedical Engineering (Y.Q., G.L., S.R.), Department of Developmental Biology (C.L., S.B., S.R.), Department of Pediatrics (K.V.W.), and Department of Cell Biology (C.G.N.), Washington University in St Louis, MO; Department of Medicine, University of Chicago, IL (R.G.); and Department of Biomedical Engineering, The George Washington University, Science and Engineering Hall, Washington DC (Y.Q., I.R.E.).
Colin G NicholsFrom the Department of Medicine, Cardiovascular Division (Y.Q., C.L., S.H., S.B., G.L., A.K., S.R.), Department of Biomedical Engineering (Y.Q., G.L., S.R.), Department of Developmental Biology (C.L., S.B., S.R.), Department of Pediatrics (K.V.W.), and Department of Cell Biology (C.G.N.), Washington University in St Louis, MO; Department of Medicine, University of Chicago, IL (R.G.); and Department of Biomedical Engineering, The George Washington University, Science and Engineering Hall, Washington DC (Y.Q., I.R.E.).
Igor R EfimovFrom the Department of Medicine, Cardiovascular Division (Y.Q., C.L., S.H., S.B., G.L., A.K., S.R.), Department of Biomedical Engineering (Y.Q., G.L., S.R.), Department of Developmental Biology (C.L., S.B., S.R.), Department of Pediatrics (K.V.W.), and Department of Cell Biology (C.G.N.), Washington University in St Louis, MO; Department of Medicine, University of Chicago, IL (R.G.); and Department of Biomedical Engineering, The George Washington University, Science and Engineering Hall, Washington DC (Y.Q., I.R.E.).
Stacey RentschlerFrom the Department of Medicine, Cardiovascular Division (Y.Q., C.L., S.H., S.B., G.L., A.K., S.R.), Department of Biomedical Engineering (Y.Q., G.L., S.R.), Department of Developmental Biology (C.L., S.B., S.R.), Department of Pediatrics (K.V.W.), and Department of Cell Biology (C.G.N.), Washington University in St Louis, MO; Department of Medicine, University of Chicago, IL (R.G.); and Department of Biomedical Engineering, The George Washington University, Science and Engineering Hall, Washington DC (Y.Q., I.R.E.). Stacey.rentschler@wustl.edu.
University of Chicago · US

Funding

TRAINING PROGRAM IN CELLULAR AND MOLECULAR BIOLOGYT32GM007067 · NIGMS · WASHINGTON UNIVERSITY · PI TRUE-KROB, HEATHER L · 1985 to 2020
$20.4M
Role of vascular KATP channels in Alzheimer’s neurodegeneration and dementiaR35HL140024 · NHLBI · WASHINGTON UNIVERSITY · PI NICHOLS, COLIN G · 2018 to 2023
$5.9M
Pediatric Cardiovascular and Pulmonary Research Training Program.T32HL125241 · NHLBI · WASHINGTON UNIVERSITY · PI Juliane Bubeck Wardenburg, Kory J. Lavine · 2015 to 2026
$4.1M
WNT SIGNALING IN CARDIAC CONDUCTION AND ARRHYTHMOGENESISR01HL130212 · NHLBI · WASHINGTON UNIVERSITY · PI RENTSCHLER, STACEY LYNN · 2016 to 2024
$4.0M
The Role of Notch Signaling in ArrhythmogenesisK08HL107449 · NHLBI · WASHINGTON UNIVERSITY · PI RENTSCHLER, STACEY LYNN · 2011 to 2015
$660k
NHLBI NIH HHS K08 HL107449NHLBI NIH HHS R01 HL130212NHLBI NIH HHS R35 HL140024NIGMS NIH HHS T32 GM007067
6 · The paper itself

Abstract

rationaleNotch signaling programs cardiac conduction during development, and in the adult ventricle, injury-induced Notch reactivation initiates global transcriptional and epigenetic changes.

objectiveTo determine whether Notch reactivation may stably alter atrial ion channel gene expression and arrhythmia inducibility. METHODS AND

resultsTo model an injury response and determine the effects of Notch signaling on atrial electrophysiology, we transiently activate Notch signaling within adult myocardium using a doxycycline-inducible genetic system (inducible Notch intracellular domain [iNICD]). Significant heart rate slowing and frequent sinus pauses are observed in iNICD mice when compared with controls. iNICD mice have structurally normal atria and preserved sinus node architecture, but expression of key transcriptional regulators of sinus node and atrial conduction, including

conclusionsOur data provide evidence that Notch signaling regulates transcription factor and ion channel gene expression within adult atrial myocardium. Notch reactivation induces electrical changes, resulting in sinus bradycardia, sinus pauses, and a susceptibility to atrial arrhythmias, which contribute to a phenotype resembling sick sinus syndrome.

Indexed as

AnimalsGene ExpressionHeart Conduction SystemIon ChannelsMiceMice, TransgenicMyocardiumOrgan Culture TechniquesReceptors, NotchSick Sinus SyndromeTime FactorsTranscription FactorsIon ChannelsReceptors, NotchTranscription Factorsatrial arrhythmiaelectrophysiologyion channelsNotchsick sinus syndrome

Identifiers

PMID28674041
PMCPMC5565396
OpenAlexW2728071739

What OpenQuestion holds

Textmetadata
LicenceTDM
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.