Show simple item record

dc.contributor.authorHerrer, I.
dc.contributor.authorRoselló-Lletí, E.
dc.contributor.authorOrtega, A.
dc.contributor.authorTarazón, E.
dc.contributor.authorMolina-Navarro, M. M.
dc.contributor.authorTriviño, J. C.
dc.contributor.authorMartínez-Dolz, L.
dc.contributor.authorAlmenar, L.
dc.contributor.authorLago Paz, Francisca 
dc.contributor.authorSánchez-Lázaro, I.
dc.contributor.authorGonzález Juanatey, José Ramón 
dc.contributor.authorSalvador, A.
dc.contributor.authorPortolés, M.
dc.date.accessioned2017-06-07T07:35:11Z
dc.date.available2017-06-07T07:35:11Z
dc.date.issued2015
dc.identifier.issn1755-8794
dc.identifier.urihttp://hdl.handle.net/20.500.11940/8240
dc.description.abstractBACKGROUND: Ischemic 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. METHODS: Myocardial tissue explants from ICM patients and control (CNT) subjects were analyzed by RNA-Sequencing (RNA-Seq) and quantitative Real-Time PCR. RESULTS: Enrichment 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). CONCLUSIONS: Our 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.
dc.description.sponsorshipNational Institute of Health "Fondo de Investigaciones Sanitarias del Instituto de Salud Carlos III"
dc.description.sponsorshipEuropean Commission
dc.language.isoeng
dc.rightsAtribución 4.0 Internacional
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshAntigens, Nuclear
dc.subject.meshApoptosis
dc.subject.meshAutoantigens
dc.subject.meshB-Cell Lymphoma 3 Protein
dc.subject.meshCCAAT-Enhancer-Binding Protein-delta
dc.subject.meshCardiomyopathies
dc.subject.meshFemale
dc.subject.meshGene Expression Profiling
dc.subject.meshGene Expression Regulation
dc.subject.meshHumans
dc.subject.meshMale
dc.subject.meshMiddle Aged
dc.subject.meshMyocardial Ischemia
dc.subject.meshMyocardium/pathology
dc.subject.meshPrincipal Component Analysis
dc.subject.meshProto-Oncogene Proteins
dc.subject.meshReal-Time Polymerase Chain Reaction
dc.subject.meshRepressor Proteins
dc.subject.meshSequence Analysis, RNA
dc.subject.meshTrans-Activators
dc.subject.meshTranscription Factors
dc.subject.meshTranscription, Genetic
dc.subject.meshTranscriptome
dc.titleGene expression network analysis reveals new transcriptional regulators as novel factors in human ischemic cardiomyopathy
dc.typeArtigoes
dc.authorsophosHerrer, I.
dc.authorsophosRoselló-Lletí, E.
dc.authorsophosOrtega, A.
dc.authorsophosTarazón, E.
dc.authorsophosMolina-Navarro, M. M.
dc.authorsophosTriviño, J. C.
dc.authorsophosMartínez-Dolz, L.
dc.authorsophosAlmenar, L.
dc.authorsophosLago, F.
dc.authorsophosSánchez-Lázaro, I.
dc.authorsophosGonzález-Juanatey, J. R.
dc.authorsophosSalvador, A.
dc.authorsophosPortolés, M.
dc.authorsophosRivera, M.
dc.identifier.doi10.1186/s12920-015-0088-y
dc.identifier.sophos19584
dc.issue.number1
dc.journal.titleBMC Medical Genomics
dc.organizationServizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::EOXI de Santiago - Complexo Hospitalario Universitario de Santiago::Cardioloxía
dc.organizationServizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::EOXI de Santiago::IDIS.- Instituto de investigaciones sanitarias de Santiago
dc.relation.projectIDISCIII/FIS/RD12/0042/0003
dc.relation.projectIDISCIII/FIS/RD06/003/1001
dc.relation.projectIDISCIII/FIS/PI10/00275
dc.relation.projectIDISCIII/FIS/PI13/00100
dc.rights.accessRightsopenAccess
dc.typesophosArtículo Original
dc.volume.number8


Files in this item

This item appears in the following Collection(s)

Show simple item record

Atribución 4.0 Internacional
Except where otherwise noted, this item's license is described as Atribución 4.0 Internacional