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miRNAs may play a major role in the control of gene expression in key pathobiological processes in Chagas disease cardiomyopathy

Chronic Chagas disease cardiomyopathy (CCC), an especially aggressive inflammatory dilated cardiomyopathy caused by lifelong infection with the protozoan Trypanosoma cruzi, is a major cause of cardiomyopathy in Latin America. Although chronic myocarditis may play a major pathogenetic role, little is...

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Autores principales: Laugier, Laurie, Ferreira, Ludmila Rodrigues Pinto, Ferreira, Frederico Moraes, Cabantous, Sandrine, Frade, Amanda Farage, Nunes, Joao Paulo, Ribeiro, Rafael Almeida, Brochet, Pauline, Teixeira, Priscila Camillo, Santos, Ronaldo Honorato Barros, Bocchi, Edimar A., Bacal, Fernando, Cândido, Darlan da Silva, Maso, Vanessa Escolano, Nakaya, Helder I., Kalil, Jorge, Cunha-Neto, Edecio, Chevillard, Christophe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787679/
https://www.ncbi.nlm.nih.gov/pubmed/33351798
http://dx.doi.org/10.1371/journal.pntd.0008889
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author Laugier, Laurie
Ferreira, Ludmila Rodrigues Pinto
Ferreira, Frederico Moraes
Cabantous, Sandrine
Frade, Amanda Farage
Nunes, Joao Paulo
Ribeiro, Rafael Almeida
Brochet, Pauline
Teixeira, Priscila Camillo
Santos, Ronaldo Honorato Barros
Bocchi, Edimar A.
Bacal, Fernando
Cândido, Darlan da Silva
Maso, Vanessa Escolano
Nakaya, Helder I.
Kalil, Jorge
Cunha-Neto, Edecio
Chevillard, Christophe
author_facet Laugier, Laurie
Ferreira, Ludmila Rodrigues Pinto
Ferreira, Frederico Moraes
Cabantous, Sandrine
Frade, Amanda Farage
Nunes, Joao Paulo
Ribeiro, Rafael Almeida
Brochet, Pauline
Teixeira, Priscila Camillo
Santos, Ronaldo Honorato Barros
Bocchi, Edimar A.
Bacal, Fernando
Cândido, Darlan da Silva
Maso, Vanessa Escolano
Nakaya, Helder I.
Kalil, Jorge
Cunha-Neto, Edecio
Chevillard, Christophe
author_sort Laugier, Laurie
collection PubMed
description Chronic Chagas disease cardiomyopathy (CCC), an especially aggressive inflammatory dilated cardiomyopathy caused by lifelong infection with the protozoan Trypanosoma cruzi, is a major cause of cardiomyopathy in Latin America. Although chronic myocarditis may play a major pathogenetic role, little is known about the molecular mechanisms responsible for its severity. The aim of this study is to study the genes and microRNAs expression in tissues and their connections in regards to the pathobiological processes. To do so, we integrated for the first time global microRNA and mRNA expression profiling from myocardial tissue of CCC patients employing pathways and network analyses. We observed an enrichment in biological processes and pathways associated with the immune response and metabolism. IFNγ, TNF and NFkB were the top upstream regulators. The intersections between differentially expressed microRNAs and differentially expressed target mRNAs showed an enrichment in biological processes such as Inflammation, inflammation, Th1/IFN-γ-inducible genes, fibrosis, hypertrophy, and mitochondrial/oxidative stress/antioxidant response. MicroRNAs also played a role in the regulation of gene expression involved in the key cardiomyopathy-related processes fibrosis, hypertrophy, myocarditis and arrhythmia. Significantly, a discrete number of differentially expressed microRNAs targeted a high number of differentially expressed mRNAs (>20) in multiple processes. Our results suggest that miRNAs orchestrate expression of multiple genes in the major pathophysiological processes in CCC heart tissue. This may have a bearing on pathogenesis, biomarkers and therapy.
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spelling pubmed-77876792021-01-14 miRNAs may play a major role in the control of gene expression in key pathobiological processes in Chagas disease cardiomyopathy Laugier, Laurie Ferreira, Ludmila Rodrigues Pinto Ferreira, Frederico Moraes Cabantous, Sandrine Frade, Amanda Farage Nunes, Joao Paulo Ribeiro, Rafael Almeida Brochet, Pauline Teixeira, Priscila Camillo Santos, Ronaldo Honorato Barros Bocchi, Edimar A. Bacal, Fernando Cândido, Darlan da Silva Maso, Vanessa Escolano Nakaya, Helder I. Kalil, Jorge Cunha-Neto, Edecio Chevillard, Christophe PLoS Negl Trop Dis Research Article Chronic Chagas disease cardiomyopathy (CCC), an especially aggressive inflammatory dilated cardiomyopathy caused by lifelong infection with the protozoan Trypanosoma cruzi, is a major cause of cardiomyopathy in Latin America. Although chronic myocarditis may play a major pathogenetic role, little is known about the molecular mechanisms responsible for its severity. The aim of this study is to study the genes and microRNAs expression in tissues and their connections in regards to the pathobiological processes. To do so, we integrated for the first time global microRNA and mRNA expression profiling from myocardial tissue of CCC patients employing pathways and network analyses. We observed an enrichment in biological processes and pathways associated with the immune response and metabolism. IFNγ, TNF and NFkB were the top upstream regulators. The intersections between differentially expressed microRNAs and differentially expressed target mRNAs showed an enrichment in biological processes such as Inflammation, inflammation, Th1/IFN-γ-inducible genes, fibrosis, hypertrophy, and mitochondrial/oxidative stress/antioxidant response. MicroRNAs also played a role in the regulation of gene expression involved in the key cardiomyopathy-related processes fibrosis, hypertrophy, myocarditis and arrhythmia. Significantly, a discrete number of differentially expressed microRNAs targeted a high number of differentially expressed mRNAs (>20) in multiple processes. Our results suggest that miRNAs orchestrate expression of multiple genes in the major pathophysiological processes in CCC heart tissue. This may have a bearing on pathogenesis, biomarkers and therapy. Public Library of Science 2020-12-22 /pmc/articles/PMC7787679/ /pubmed/33351798 http://dx.doi.org/10.1371/journal.pntd.0008889 Text en © 2020 Laugier et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Laugier, Laurie
Ferreira, Ludmila Rodrigues Pinto
Ferreira, Frederico Moraes
Cabantous, Sandrine
Frade, Amanda Farage
Nunes, Joao Paulo
Ribeiro, Rafael Almeida
Brochet, Pauline
Teixeira, Priscila Camillo
Santos, Ronaldo Honorato Barros
Bocchi, Edimar A.
Bacal, Fernando
Cândido, Darlan da Silva
Maso, Vanessa Escolano
Nakaya, Helder I.
Kalil, Jorge
Cunha-Neto, Edecio
Chevillard, Christophe
miRNAs may play a major role in the control of gene expression in key pathobiological processes in Chagas disease cardiomyopathy
title miRNAs may play a major role in the control of gene expression in key pathobiological processes in Chagas disease cardiomyopathy
title_full miRNAs may play a major role in the control of gene expression in key pathobiological processes in Chagas disease cardiomyopathy
title_fullStr miRNAs may play a major role in the control of gene expression in key pathobiological processes in Chagas disease cardiomyopathy
title_full_unstemmed miRNAs may play a major role in the control of gene expression in key pathobiological processes in Chagas disease cardiomyopathy
title_short miRNAs may play a major role in the control of gene expression in key pathobiological processes in Chagas disease cardiomyopathy
title_sort mirnas may play a major role in the control of gene expression in key pathobiological processes in chagas disease cardiomyopathy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787679/
https://www.ncbi.nlm.nih.gov/pubmed/33351798
http://dx.doi.org/10.1371/journal.pntd.0008889
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