Evidence map›Paper›PMID 25884818›Full record

ArticleBMC medical genomics2015

Gene expression network analysis reveals new transcriptional regulators as novel factors in human ischemic cardiomyopathy.

Isabel Herrer, Esther Roselló-Lletí, Ana Ortega, Estefanía Tarazón, María Micaela Molina-Navarro, Juan Carlos Triviño, Luis Martínez-Dolz, Luis Almenar, Francisca Lago, Ignacio Sánchez-Lázaro and 4 more

Open access · goldAbstract read
In one paragraph

Article in BMC medical genomics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 17% 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

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.

  1. Pooled it
  2. Unveiling the multifaceted roles of BCL3: biological functions and disease implications.Apoptosis : an international journal on programmed cell death · 2026
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  10. Comprehensive Analysis of Cardiac Xeno-Graft Unveils Rejection Mechanisms.International journal of molecular sciences · 2021
    Article
  11. Frontiers in genetics · 2021
    Article
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  15. Article
  16. Article
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  19. Article
  20. p53 regulates the cardiac transcriptome.Proceedings of the National Academy of Sciences of the United States of America · 2017
    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

14 authors at 2 institutions in 1 country.

Isabel HerrerCardiocirculatory Unit, Health Research Institute of La Fe University Hospital, Avd de Fernando Abril Martorell, 106, 46026, Valencia, Spain. isaherrer@gmail.com.
Esther Roselló-LletíCardiocirculatory Unit, Health Research Institute of La Fe University Hospital, Avd de Fernando Abril Martorell, 106, 46026, Valencia, Spain. esther_rosello_lleti@hotmail.com.
Ana OrtegaCardiocirculatory Unit, Health Research Institute of La Fe University Hospital, Avd de Fernando Abril Martorell, 106, 46026, Valencia, Spain. anaortegagutierrez@hotmail.com.
Estefanía TarazónCardiocirculatory Unit, Health Research Institute of La Fe University Hospital, Avd de Fernando Abril Martorell, 106, 46026, Valencia, Spain. estamel@alumni.uv.es.
María Micaela Molina-NavarroCardiocirculatory Unit, Health Research Institute of La Fe University Hospital, Avd de Fernando Abril Martorell, 106, 46026, Valencia, Spain. micaela.molina.navarro@googlemail.com.
Juan Carlos TriviñoGenomic Systems, Paterna, Valencia, Spain. jc.trivino@sistemasgenomicos.com.
Luis Martínez-DolzHeart Failure and Transplantation Unit, Cardiology Department, La Fe University Hospital, Valencia, Spain. lmartinezd@meditex.es.
Luis AlmenarHeart Failure and Transplantation Unit, Cardiology Department, La Fe University Hospital, Valencia, Spain. lualmenar@gmail.com.
Francisca LagoCellular and Molecular Cardiology Unit, Department of Cardiology and Institute of Biomedical Research, University Clinical Hospital, Santiago Compostela, Spain. francisca.lago.paz@sergas.es.
Ignacio Sánchez-LázaroHeart Failure and Transplantation Unit, Cardiology Department, La Fe University Hospital, Valencia, Spain. ignaciosanchezlazaro@gmail.com.
José Ramón González-JuanateyCellular and Molecular Cardiology Unit, Department of Cardiology and Institute of Biomedical Research, University Clinical Hospital, Santiago Compostela, Spain. jose.ramon.gonzalez.juanatey@sergas.es.
Antonio SalvadorHeart Failure and Transplantation Unit, Cardiology Department, La Fe University Hospital, Valencia, Spain. salvador_ant@gva.es.
Manuel PortolésCardiocirculatory Unit, Health Research Institute of La Fe University Hospital, Avd de Fernando Abril Martorell, 106, 46026, Valencia, Spain. portoles_man@gva.es.
Miguel RiveraCardiocirculatory Unit, Health Research Institute of La Fe University Hospital, Avd de Fernando Abril Martorell, 106, 46026, Valencia, Spain. miguelrivera492@gmail.com.
Hospital Universitari i Politècnic La Fe · ESSistemas Genómicos · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIschemic cardiomyopathy (ICM) is characterized by transcriptomic changes that alter cellular processes leading to decreased cardiac output. Because the molecular network of ICM is largely unknown, the aim of this study was to characterize the role of new transcriptional regulators in the molecular mechanisms underlying the responses to ischemia.

methodsMyocardial tissue explants from ICM patients and control (CNT) subjects were analyzed by RNA-Sequencing (RNA-Seq) and quantitative Real-Time PCR.

resultsEnrichment analysis of the ICM transcriptomic profile allowed the characterization of novel master regulators. We found that the expression of the transcriptional regulators SP100 (-1.5-fold, p < 0.05), CITED2 (-3.8-fold, p < 0.05), CEBPD (-4.9-fold, p < 0.05) and BCL3 (-3.3-fold, p < 0.05) were lower in ICM than in CNT. To gain insights into the molecular network defined by the transcription factors, we identified CEBPD, BCL3, and HIF1A target genes in the RNA-Seq datasets. We further characterized the biological processes of the target genes by gene ontology annotation. Our results suggest that CEBPD-inducible genes with roles in the inhibition of apoptosis are downregulated and that BCL3-repressible genes are involved in the regulation of cellular metabolism in ICM. Moreover, our results suggest that CITED2 downregulation causes increased expression of HIF1A target genes. Functional analysis of HIF1A target genes revealed that hypoxic and stress response genes are activated in ICM. Finally, we found a significant correlation between the mRNA levels of BCL3 and the mRNA levels of both CEBPD (r = 0.73, p < 0.001) and CITED2 (r = 0.56, p < 0.05). Interestingly, CITED2 mRNA levels are directly related to ejection fraction (EF) (r = 0.54, p < 0.05).

conclusionsOur data indicate that changes in the expression of SP100, CITED2, CEBPD, and BCL3 affect their transcription regulatory networks, which subsequently alter a number of biological processes in ICM patients. The relationship between CITED2 mRNA levels and EF emphasizes the importance of this transcription factor in ICM. Moreover, our findings identify new mechanisms used to interpret gene expression changes in ICM and provide valuable resources for further investigation of the molecular basis of human cardiac ischemic response.

Indexed as

Gene Expression ProfilingTranscription, GeneticAdultAgedAntigens, NuclearApoptosisAutoantigensB-Cell Lymphoma 3 ProteinCardiomyopathiesCCAAT-Enhancer-Binding Protein-deltaFemaleGene Expression RegulationHumansMaleMiddle AgedMyocardial IschemiaAntigens, NuclearAutoantigensB-Cell Lymphoma 3 ProteinBCL3 protein, humanCCAAT-Enhancer-Binding Protein-deltaCEBPD protein, humanCITED2 protein, humanProto-Oncogene ProteinsRepressor ProteinsSP100 protein, humanTrans-ActivatorsTranscription Factors

Identifiers

PMID25884818
PMCPMC4386080
OpenAlexW1973883521

What OpenQuestion holds

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LicenceCC BY
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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.