Evidence map›Paper›PMID 31834445›Full record

ArticleJournal of molecular medicine (Berlin, Germany)2019

Gene-environment regulatory circuits of right ventricular pathology in tetralogy of fallot.

Yan Zhao, Xuedong Kang, Fuying Gao, Alejandra Guzman, Ryan P Lau, Reshma Biniwale, Madhuri Wadehra, Brian Reemtsen, Meena Garg, Nancy Halnon and 6 more

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

Article in Journal of molecular medicine (Berlin, Germany), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.0field-weighted citation impact, top 23% 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

9 citing papers in PubMed, 18 citations in OpenAlex.

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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

16 authors at 1 institution in 2 countries.

Yan ZhaoDepartment of Pediatrics, David Geffen School of Medicine, University of California, 10833 Le Conte Ave, MDCC-B2-375, Los Angeles, CA, 90095, USA.
Xuedong KangDepartment of Pediatrics, David Geffen School of Medicine, University of California, 10833 Le Conte Ave, MDCC-B2-375, Los Angeles, CA, 90095, USA.
Fuying GaoDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Alejandra GuzmanDepartment of Pediatrics, David Geffen School of Medicine, University of California, 10833 Le Conte Ave, MDCC-B2-375, Los Angeles, CA, 90095, USA.
Ryan P LauDepartment of Pathology and Laboratory Medicine, Clinical Genomics Center, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Reshma BiniwaleDepartment of Cardiothoracic Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Madhuri WadehraDepartment of Pathology and Laboratory Medicine, Clinical Genomics Center, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Brian ReemtsenDepartment of Cardiothoracic Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Meena GargDepartment of Pediatrics, David Geffen School of Medicine, University of California, 10833 Le Conte Ave, MDCC-B2-375, Los Angeles, CA, 90095, USA.
Nancy HalnonDepartment of Pediatrics, David Geffen School of Medicine, University of California, 10833 Le Conte Ave, MDCC-B2-375, Los Angeles, CA, 90095, USA.
Fabiola Quintero-RiveraDepartment of Pathology and Laboratory Medicine, Clinical Genomics Center, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Glen Van ArsdellDepartment of Cardiothoracic Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Giovanni CoppolaDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Stanley F NelsonDepartment of Pediatrics, David Geffen School of Medicine, University of California, 10833 Le Conte Ave, MDCC-B2-375, Los Angeles, CA, 90095, USA.
Marlin ToumaDepartment of Pediatrics, David Geffen School of Medicine, University of California, 10833 Le Conte Ave, MDCC-B2-375, Los Angeles, CA, 90095, USA. mtouma@mednet.ucla.edu.ORCID 0000-0002-2827-4068
UCLA Congenital Heart Defects BioCore Faculty
University of California, Los Angeles · US

Funding

Integrative Center for Neurogenetics and Neurogenomics - OverallP30NS062691 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI COPPOLA, GIOVANNI · 2009 to 2018
$7.4M
Novel Gene-Environment Regulatory Circuit in Chamber-Specific Growth of Perinatal HeartR01HL153853 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TOUMA, MARLIN · 2020 to 2023
$1.6M
Novel Gene-Environment Regulatory Circuit in Chamber Specific Growth of Perinatal HeartR56HL146738 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TOUMA, MARLIN · 2019 to 2019
$390k
NHLBI NIH HHS R01 HL153853NHLBI NIH HHS R56 HL146738NINDS NIH HHS P30 NS062691
6 · The paper itself

Abstract

The phenotypic spectrum of congenital heart defects (CHDs) is contributed by both genetic and environmental factors. Their interactions are profoundly heterogeneous but may operate on common pathways as in the case of hypoxia signaling during postnatal heart development in the context of CHDs. Tetralogy of Fallot (TOF) is the most common cyanotic (hypoxemic) CHD. However, how the hypoxic environment contributes to TOF pathogenesis after birth is poorly understood. We performed Genome-wide transcriptome analysis on right ventricle outflow tract (RVOT) specimens from cyanotic and noncyanotic TOF. Co-expression network analysis identified gene modules specifically associated with clinical diagnosis and hypoxemia status in the TOF hearts. In particular, hypoxia-dependent induction of myocyte proliferation is associated with E2F1-mediated cell cycle regulation and repression of the WNT11-RB1 axis. Genes enriched in epithelial mesenchymal transition (EMT), fibrosis, and sarcomere were also repressed in cyanotic TOF patients. Importantly, transcription factor analysis of the hypoxia-regulated modules suggested CREB1 as a putative regulator of hypoxia/WNT11-RB1 circuit. The study provides a high-resolution landscape of transcriptome programming associated with TOF phenotypes and unveiled hypoxia-induced regulatory circuit in cyanotic TOF. Hypoxia-induced cardiomyocyte proliferation involves negative modulation of CREB1 activity upstream of the WNT11-RB1 axis. KEY MESSAGES: Genetic and environmental factors contribute to congenital heart defects (CHDs). How hypoxia contributes to Tetralogy of Fallot (TOF) pathogenesis after birth is unclear. Systems biology-based analysis revealed distinct molecular signature in CHDs. Gene expression modules specifically associated with cyanotic TOF were uncovered. Key regulatory circuits induced by hypoxia in TOF pathogenesis after birth were unveiled.

Indexed as

ChildChild, PreschoolCohort StudiesCyclic AMP Response Element-Binding ProteinE2F1 Transcription FactorEpithelial-Mesenchymal TransitionFemaleGene Expression ProfilingGene Expression RegulationGene Regulatory NetworksGenomeHeart VentriclesHumansHypoxiaInfantMaleCREB1 protein, humanCyclic AMP Response Element-Binding ProteinE2F1 protein, humanE2F1 Transcription FactorWnt11 protein, humanWnt ProteinsCongenital heart defectsGenomeHypoxiaTetralogy of FallotTranscriptome

Identifiers

PMID31834445
PMCPMC7942233
OpenAlexW2996280142

What OpenQuestion holds

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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.