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

authors

  • 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

keywords

  • MicroRNAs
  • Gene expression
  • Myocardium
  • Inflammation
  • Fibrosis
  • Cytokines
  • Principal component analysis
  • Mitochondria

document type

ART

abstract

Chronic Chagas disease cardiomyopathy (CCC), an aggressive dilated cardiomyopathy caused by Trypanosoma cruzi, is a major cause of cardiomyopathy in Latin America. Little is known about the molecular mechanisms responsible for its severity. Authors study the possible role of microRNAs in the regulation of gene expression in relevant pathways and pathobiological processes. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs)-small RNAs that can regulate gene expression-associated to severe cardiomyopathy development. The inflammatory mediator Interferon-γ was the most likely inducer of gene expression in CCC, and most genes belonged to the immune response, fibrosis, hypertrophy and mitochondrial metabolism. A discrete number of differentially expressed mRNAs targeted a high number of differentially expressed mRNAs in multiple processes. Moreover, several pathways had multiple targets regulated by microRNAs, suggesting synergic effect. Results suggest that microRNAs orchestrate expression of multiple genes in the major pathophysiological processes in CCC heart tissue.

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