title: Novel insights into the development of chagasic cardiomyopathy: role of PI3Kinase/NO axis.
abstract: BACKGROUND
  Chagas' disease is one of the leading causes of heart failure in Latin American countries. Despite its great social impact, there is no direct evidence in the literature explaining the development of heart failure in Chagas' disease. Therefore, the main objective of the study was to investigate the development of the Chagas' disease towards its chronic phase and correlate with modifications in the cellular electrophysiological characteristics of the infected heart.
  
  
  RESULTS
  Using a murine model of Chagas' disease, we confirmed and extended previous findings of altered electrocardiogram and echocardiogram in this cardiomyopathy. The observed changes in the electrocardiogram were correlated with the prolonged action potential and reduced transient outward potassium current density. Reduced heart function was associated with remodeling of intracellular calcium handling, altered extracellular matrix content, and to a set of proteins involved in the control of cellular contractility in ventricular myocytes. Furthermore, disruption of calcium homeostasis was partially due to activation of the PI3Kinase/nitric oxide signaling pathway. Finally, we propose a causal link between the inflammatory mediators and heart remodeling during chagasic cardiomyopathy.
  
  
  CONCLUSIONS
  Altogether our results demonstrate that heart failure in Chagas' disease may occur due to electrical and mechanical remodeling of cardiac myocytes, and suggest that AKT/PI3K/NO axis could be an important pharmacological target to improve the disease outcome.
authors.affiliation: Laboratórios de Membranas Excitáveis e de Biologia Cardiovascular, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. drcbio@gmail.com
authors.forename: Danilo
authors.initials: D
authors.lastname: Roman-Campos
authors.forename: Policarpo
authors.initials: P
authors.lastname: Sales-Junior
authors.forename: Hugo L
authors.initials: HL
authors.lastname: Duarte
authors.forename: Enéas R
authors.initials: ER
authors.lastname: Gomes
authors.forename: Aline
authors.initials: A
authors.lastname: Lara
authors.forename: Paula
authors.initials: P
authors.lastname: Campos
authors.forename: Nazareth N
authors.initials: NN
authors.lastname: Rocha
authors.forename: Rodrigo R
authors.initials: RR
authors.lastname: Resende
authors.forename: Anderson
authors.initials: A
authors.lastname: Ferreira
authors.forename: Sílvia
authors.initials: S
authors.lastname: Guatimosim
authors.forename: Ricardo T
authors.initials: RT
authors.lastname: Gazzinelli
authors.forename: Catherine
authors.initials: C
authors.lastname: Ropert
authors.forename: Jader S
authors.initials: JS
authors.lastname: Cruz
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002598:Chagas Cardiomyopathy / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000469:parasitology; D009569:Nitric Oxide / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D014349:Trypanosoma cruzi / Q000502:physiology
chemical_list: D009569:Nitric Oxide; D019869:Phosphatidylinositol 3-Kinases