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. METHODS AND 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. CONCLUSION: 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.
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. METHODS AND 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. CONCLUSION: 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: Alexandre J S Ribeiro; Olivier Schwab; Mohammad A Mandegar; Yen-Sin Ang; Bruce R Conklin; Deepak Srivastava; Beth L Pruitt Journal: Circ Res Date: 2017-04-11 Impact factor: 17.367
Authors: Eduardo Ov Curvo; Roberto R Ferreira; Fabiana S Madeira; Gabriel F Alves; Mayara C Chambela; Veronica G Mendes; Luiz Henrique C Sangenis; Mariana C Waghabi; Roberto M Saraiva Journal: Mem Inst Oswaldo Cruz Date: 2018-02-19 Impact factor: 2.743
Authors: Maria C Silva; Marcela Davoli-Ferreira; Tiago S Medina; Renata Sesti-Costa; Grace K Silva; Carla D Lopes; Lucas E Cardozo; Fábio N Gava; Konstantina Lyroni; Fabrício C Dias; Amanda F Frade; Monique Baron; Helder I Nakaya; Florêncio Figueiredo; José C Alves-Filho; Fernando Q Cunha; Christos Tsatsanis; Christophe Chevillard; Edecio Cunha-Neto; Emilio Hirsch; João S Silva; Thiago M Cunha Journal: Nat Commun Date: 2018-04-17 Impact factor: 14.919
Authors: Danilo Roman-Campos; Policarpo Sales-Junior; Alexandre D Costa; Diego Santos Souza; Artur Santos-Miranda; Julliane V Joviano-Santos; Catherine Ropert; Jader S Cruz Journal: Microorganisms Date: 2022-01-25