Evidence map›Paper›PMID 32533200›Full record

ArticleJournal of molecular medicine (Berlin, Germany)2020

Gene-environment regulation of chamber-specific maturation during hypoxemic perinatal circulatory transition.

Yan Zhao, Xuedong Kang, Alexander Barsegian, Jian He, Alejandra Guzman, Ryan P Lau, Reshma Biniwale, Madhuri Wadhra, Brian Reemtsen, Meena Garg and 7 more

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

Article in Journal of molecular medicine (Berlin, Germany), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact, top 95% 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

0 citing papers in PubMed, 1 citations in OpenAlex.

No citing paper in PubMed yet.

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

17 authors at 1 institution in 1 country.

Yan Zhao *Department of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles 675 Charles E. Young Dr S, 3762 MacDonald Research Laboratories, Los Angeles, CA, 90024, USA.
Xuedong Kang *Department of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles 675 Charles E. Young Dr S, 3762 MacDonald Research Laboratories, Los Angeles, CA, 90024, USA.
Alexander BarsegianDepartment of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles 675 Charles E. Young Dr S, 3762 MacDonald Research Laboratories, Los Angeles, CA, 90024, USA.
Jian HeDepartment of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles 675 Charles E. Young Dr S, 3762 MacDonald Research Laboratories, Los Angeles, CA, 90024, USA.
Alejandra GuzmanDepartment of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles 675 Charles E. Young Dr S, 3762 MacDonald Research Laboratories, Los Angeles, CA, 90024, USA.
Ryan P LauDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Reshma BiniwaleDepartment of Cardiothoracic Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Madhuri WadhraDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Brian ReemtsenDepartment of Cardiothoracic Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Meena GargDepartment of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles 675 Charles E. Young Dr S, 3762 MacDonald Research Laboratories, Los Angeles, CA, 90024, USA.
Nancy HalnonDepartment of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles 675 Charles E. Young Dr S, 3762 MacDonald Research Laboratories, Los Angeles, CA, 90024, USA.
Fabiola Quintero-RiveraDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Wayne W GrodyDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
UCLA Congenital Heart Defects BioCore Faculty
Glen Van ArsdellDepartment of Cardiothoracic Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Stanley F NelsonDepartment of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles 675 Charles E. Young Dr S, 3762 MacDonald Research Laboratories, Los Angeles, CA, 90024, USA.
Marlin ToumaDepartment of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles 675 Charles E. Young Dr S, 3762 MacDonald Research Laboratories, Los Angeles, CA, 90024, USA. mtouma@mednet.ucla.edu.ORCID http://orcid.org/0000-0002-2827-4068
University of California, Los Angeles · US

Funding

UCLA Child Health Research Career Development AwardK12HD034610 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DEVASKAR, SHERIN U · 2002 to 2017
$6.6M
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 HL146738NICHD NIH HHS K12 HD034610NIH/NHLBI 1R56HL146738-01
6 · The paper itself

Abstract

Chamber-specific and temporally regulated perinatal cardiac growth and maturation is critical for functional adaptation of the heart and may be altered significantly in response to perinatal stress, such as systemic hypoxia (hypoxemia), leading to significant pathology, even mortality. Understanding transcriptome regulation of neonatal heart chambers in response to hypoxemia is necessary to develop chamber-specific therapies for infants with cyanotic congenital heart defects (CHDs). We sought to determine chamber-specific transcriptome programming during hypoxemic perinatal circulatory transition. We performed transcriptome-wide analysis on right ventricle (RV) and left ventricle (LV) of postnatal day 3 (P3) mouse hearts exposed to perinatal hypoxemia. Hypoxemia decreased baseline differences between RV and LV leading to significant attenuation of ventricular patterning (AVP), which involved several molecular pathways, including Wnt signaling suppression and cell cycle induction. Notably, robust changes in RV transcriptome in hypoxemic condition contributed significantly to the AVP. Remarkably, suppression of epithelial mesenchymal transition (EMT) and dysregulation of the TP53 signaling were prominent hallmarks of the AVP genes in neonatal mouse heart. Furthermore, members of the TP53-related gene family were dysregulated in the hypoxemic RVs of neonatal mouse and cyanotic Tetralogy of Fallot hearts. Integrated analysis of chamber-specific transcriptome revealed hypoxemia-specific changes that were more robust in RVs compared with LVs, leading to previously uncharacterized AVP induced by perinatal hypoxemia. Remarkably, reprogramming of EMT process and dysregulation of the TP53 network contributed to transcriptome remodeling of neonatal heart during hypoxemic circulatory transition. These insights may enhance our understanding of hypoxemia-induced pathogenesis in newborn infants with cyanotic CHD phenotypes. KEY MESSAGES: During perinatal circulatory transition, transcriptome programming is a major driving force of cardiac chamber-specific maturation and adaptation to hemodynamic load and external environment. During hypoxemic perinatal transition, transcriptome reprogramming may affect chamber-specific growth and development, particularly in newborns with congenital heart defects (CHDs). Chamber-specific transcriptome changes during hypoxemic perinatal transition are yet to be fully elucidated. Systems-based analysis of hypoxemic neonatal hearts at postnatal day 3 reveals chamber-specific transcriptome signatures during hypoxemic perinatal transition, which involve attenuation of ventricular patterning (AVP) and repression of epithelial mesenchymal transition (EMT). Key regulatory circuits involved in hypoxemia response were identified including suppression of Wnt signaling, induction of cellular proliferation and dysregulation of TP53 network.

Indexed as

AnimalsAnimals, NewbornCell ProliferationEpithelial-Mesenchymal TransitionFemaleGene Expression ProfilingHeart Defects, CongenitalHeart VentriclesHypoxiaMaleMiceMice, Inbred C57BLSignal TransductionTranscriptomeCongenital heart defectsHypoxiaNeonatal heart maturationTetralogy of FallotTranscriptome

Identifiers

PMID32533200
PMCPMC7843236
OpenAlexW3034310349

What Socratic 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 Socratic graph.