Evidence map›Paper›PMID 20920545›Full record

ArticleToxicology2011

Gene expression profiling of DEHP-treated cardiomyocytes reveals potential causes of phthalate arrhythmogenicity.

Nikki Gillum Posnack, Norman H Lee, Ronald Brown, Narine Sarvazyan

Open access · greenAbstract readValidation Study
In one paragraph

Article in Toxicology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
0.8field-weighted citation impact, top 28% 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

25 citing papers in PubMed, 59 citations in OpenAlex.

  1. Article
  2. Article
  3. Evidence for the cardiodepressive effects of the plasticizer di-2-ethylhexyl phthalate.Toxicological sciences : an official journal of the Society of Toxicology · 2023
    Article
  4. Article
  5. Article
  6. Article
  7. Chronic perinatal hypoxia delays cardiac maturation in a mouse model for cyanotic congenital heart disease.American journal of physiology. Heart and circulatory physiology · 2021
    Article
  8. Review
  9. Phthalates Implications in the Cardiovascular System.Journal of cardiovascular development and disease · 2020
    Review
  10. Article
  11. Di (2-ethylhexyl) phthalate induces cardiac disorders in BALB/c mice.Environmental science and pollution research international · 2019
    Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article
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

4 authors at 2 institutions in 1 country.

Nikki Gillum PosnackThe Pharmacology & Physiology Department, The George Washington University, 2300 Eye Street, Washington, DC 20037, USA.
Norman H Lee
Ronald Brown
Narine Sarvazyan
George Washington University · USCenter for Devices and Radiological Health · US

Funding

Non-reentrant arrhythmias: ectopic nexus hypothesisR01HL076722 · NHLBI · TEXAS TECH UNIVERSITY HEALTH SCIS CENTER · PI SARVAZYAN, NARINE · 2004 to 2007
$1.6M
Mapping Gene Networks in Colon CancerR01CA120316 · NCI · GEORGE WASHINGTON UNIVERSITY · PI LEE, NORMAN H · 2007 to 2010
$1.6M
Low flow reperfusion after acute myocardial ischemia: when too little is too muchR01HL095828 · NHLBI · GEORGE WASHINGTON UNIVERSITY · PI KAY, MATTHEW W. · 2010 to 2014
$1.6M
The effect of phthalates on the heart: molecular pathways and clinical relevanceF32ES019057 · NIEHS · GEORGE WASHINGTON UNIVERSITY · PI POSNACK, NIKKI GILLUM · 2010 to 2013
$147k
NCI NIH HHS CA120316NCI NIH HHS R01 CA120316NHLBI NIH HHS HL076722NHLBI NIH HHS R01 HL076722NHLBI NIH HHS R01 HL095828NIEHS NIH HHS 1F32ES019057NIEHS NIH HHS F32 ES019057
6 · The paper itself

Abstract

backgroundDi-(2-ethylhexyl)-phthalate (DEHP) is a widely used plasticizer that imparts flexibility to polyvinyl chloride. We have recently reported that clinically relevant concentrations of DEHP can affect electrical coupling between cardiac myocytes causing significant rhythm disturbances. The underlying causes for this effect are currently unknown.

objectivesTo use data on global mRNA expression as a tool to reveal possible pathways leading to arrhythmogenic effects of DEHP.

methodsRat neonatal cardiomyocytes were treated with 50 μg/mL DEHP for 72 h. Extracted RNA samples were hybridized onto Affymetrix Rat Gene 1.0 ST arrays. The mRNA expression of a subset of genes was validated by qRT-PCR. In a second set of experiments, cells were treated in a concentration dependent manner to identify genes affected by low DEHP concentrations.

resultsDEHP exposure is associated with global changes in mRNA expression, with differentially expressed genes overrepresented in 47 Gene Ontology categories. Modified expression was detected for genes associated with cell electrical activity, calcium handling, adhesion and microtubular transport. For a number of key proteins, including kinesin, TGFβ2, α-tubulin, and α1 & β1 integrins, changes in mRNA levels were confirmed on the level of the protein expression. A number of genes associated with cell adhesion and electrical activity were identified as early DEHP targets as they were affected by concentrations as low as 1 μg/mL.

conclusionsExposure of neonatal rat cardiomyocytes to clinically relevant DEHP concentrations leads to global changes in mRNA expression. These changes help to explain the arrhythmogenic effects of phthalates on these cells.

Indexed as

AnimalsAnimals, NewbornArrhythmias, CardiacCell AdhesionDiethylhexyl PhthalateDose-Response Relationship, DrugGene Expression ProfilingMyocytes, CardiacPlasticizersRatsRats, Sprague-DawleyReverse Transcriptase Polymerase Chain ReactionRNA, MessengerDiethylhexyl PhthalatePlasticizersRNA, Messenger

Identifiers

PMID20920545
PMCPMC3003946
OpenAlexW2107295824

What OpenQuestion holds

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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.