Functional networks of nucleocytoplasmic transport-related genes differentiate ischemic and dilated cardiomyopathies. A new therapeutic opportunity.
Heart failure provokes alterations in the expression of nucleocytoplasmic transport-related genes. To elucidate the nucleocytoplasmic transport-linked functional network underlying the two major causes of heart failure, ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM), we examined glob...
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doaj-e0f90a122e4a483b98514a38b9eb27632020-11-25T02:22:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0198e10470910.1371/journal.pone.0104709Functional networks of nucleocytoplasmic transport-related genes differentiate ischemic and dilated cardiomyopathies. A new therapeutic opportunity.María Micaela Molina-NavarroJuan Carlos TriviñoLuis Martínez-DolzFrancisca LagoJose Ramón González-JuanateyManuel PortolésMiguel RiveraHeart failure provokes alterations in the expression of nucleocytoplasmic transport-related genes. To elucidate the nucleocytoplasmic transport-linked functional network underlying the two major causes of heart failure, ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM), we examined global transcriptome profiles of left ventricular myocardium tissue samples from 31 patients (ICM, n = 10; DCM, n = 13) undergoing heart transplantation and control donors (CNT, n = 8) using RNA-Sequencing and GeneMANIA. Comparative profiling of ICM versus control and DCM versus control showed 1081 and 2440 differentially expressed genes, respectively (>1.29-fold; P<0.05). GeneMANIA revealed differentially regulated functional networks specific to ICM and DCM. In comparison with CNT, differential expression was seen in 9 and 12 nucleocytoplasmic transport-related genes in ICM and DCM groups, respectively. DDX3X, KPNA2, and PTK2B were related to ICM, while SMURF2, NUP153, IPO5, RANBP3, NOXA1, and RHOJ were involved in DCM pathogenesis. Furthermore, the two pathologies shared 6 altered genes: XPO1, ARL4, NFKB2, FHL3, RANBP2, and RHOU showing an identical trend in expression in both ICM and DCM. Notably, the core of the derived functional networks composed of nucleocytoplasmic transport-related genes (XPO1, RANBP2, NUP153, IPO5, KPNA2, and RANBP3) branched into several pathways with downregulated genes. Moreover, we identified genes whose expression levels correlated with left ventricular mass index and left ventricular function parameters in HF patients. Collectively, our study provides a clear distinction between the two pathologies at the transcriptome level and opens up new possibilities to search for appropriate therapeutic targets for ICM and DCM.http://europepmc.org/articles/PMC4138080?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
María Micaela Molina-Navarro Juan Carlos Triviño Luis Martínez-Dolz Francisca Lago Jose Ramón González-Juanatey Manuel Portolés Miguel Rivera |
spellingShingle |
María Micaela Molina-Navarro Juan Carlos Triviño Luis Martínez-Dolz Francisca Lago Jose Ramón González-Juanatey Manuel Portolés Miguel Rivera Functional networks of nucleocytoplasmic transport-related genes differentiate ischemic and dilated cardiomyopathies. A new therapeutic opportunity. PLoS ONE |
author_facet |
María Micaela Molina-Navarro Juan Carlos Triviño Luis Martínez-Dolz Francisca Lago Jose Ramón González-Juanatey Manuel Portolés Miguel Rivera |
author_sort |
María Micaela Molina-Navarro |
title |
Functional networks of nucleocytoplasmic transport-related genes differentiate ischemic and dilated cardiomyopathies. A new therapeutic opportunity. |
title_short |
Functional networks of nucleocytoplasmic transport-related genes differentiate ischemic and dilated cardiomyopathies. A new therapeutic opportunity. |
title_full |
Functional networks of nucleocytoplasmic transport-related genes differentiate ischemic and dilated cardiomyopathies. A new therapeutic opportunity. |
title_fullStr |
Functional networks of nucleocytoplasmic transport-related genes differentiate ischemic and dilated cardiomyopathies. A new therapeutic opportunity. |
title_full_unstemmed |
Functional networks of nucleocytoplasmic transport-related genes differentiate ischemic and dilated cardiomyopathies. A new therapeutic opportunity. |
title_sort |
functional networks of nucleocytoplasmic transport-related genes differentiate ischemic and dilated cardiomyopathies. a new therapeutic opportunity. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
Heart failure provokes alterations in the expression of nucleocytoplasmic transport-related genes. To elucidate the nucleocytoplasmic transport-linked functional network underlying the two major causes of heart failure, ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM), we examined global transcriptome profiles of left ventricular myocardium tissue samples from 31 patients (ICM, n = 10; DCM, n = 13) undergoing heart transplantation and control donors (CNT, n = 8) using RNA-Sequencing and GeneMANIA. Comparative profiling of ICM versus control and DCM versus control showed 1081 and 2440 differentially expressed genes, respectively (>1.29-fold; P<0.05). GeneMANIA revealed differentially regulated functional networks specific to ICM and DCM. In comparison with CNT, differential expression was seen in 9 and 12 nucleocytoplasmic transport-related genes in ICM and DCM groups, respectively. DDX3X, KPNA2, and PTK2B were related to ICM, while SMURF2, NUP153, IPO5, RANBP3, NOXA1, and RHOJ were involved in DCM pathogenesis. Furthermore, the two pathologies shared 6 altered genes: XPO1, ARL4, NFKB2, FHL3, RANBP2, and RHOU showing an identical trend in expression in both ICM and DCM. Notably, the core of the derived functional networks composed of nucleocytoplasmic transport-related genes (XPO1, RANBP2, NUP153, IPO5, KPNA2, and RANBP3) branched into several pathways with downregulated genes. Moreover, we identified genes whose expression levels correlated with left ventricular mass index and left ventricular function parameters in HF patients. Collectively, our study provides a clear distinction between the two pathologies at the transcriptome level and opens up new possibilities to search for appropriate therapeutic targets for ICM and DCM. |
url |
http://europepmc.org/articles/PMC4138080?pdf=render |
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