Open AccessmiRNAs may play a major role in the control of gene expression in key pathobiological processes in Chagas disease cardiomyopathy
Author(s) -
Laurie Laugier,
Ludmila Rodrigues Pinto Ferreira,
Frederico Moraes Ferreira,
Stéphanie Cabantous,
Amanda Farage Frade,
João Paulo Silva Nunes,
Rodrigo Alves Ribeiro,
Pauline Brochet,
Priscila Camillo Teixeira,
Ronaldo Honorato Barros Santos,
Edimar Alcides Bocchi,
Fernando Bacal,
Darlan da Silva Cândido,
Vanessa Escolano Maso,
Helder I. Nakaya,
Jorge Kalil,
Edécio CunhaNeto,
Christophe Chevillard
Publication year - 2020
Publication title -
plos neglected tropical diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.99
H-Index - 135
eISSN - 1935-2735
pISSN - 1935-2727
DOI - 10.1371/journal.pntd.0008889
Subject(s) - microrna , biology , cardiomyopathy , inflammation , fibrosis , gene expression profiling , myocarditis , pathogenesis , gene expression , immunology , cancer research , gene , genetics , pathology , medicine , heart failure
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.