Novel insights into the development of chagasic cardiomyopathy: Role of PI3Kinase/NO axis

• Published in: International journal of cardiology Vol. 167; no. 6; pp. 3011 - 3020
• Main Authors: Roman-Campos, Danilo, Sales-Junior, Policarpo, Duarte, Hugo L, Gomes, Enéas R, Lara, Aline, Campos, Paula, Rocha, Nazareth N, Resende, Rodrigo R, Ferreira, Anderson, Guatimosim, Sílvia, Gazzinelli, Ricardo T, Ropert, Catherine, Cruz, Jader S
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 10.09.2013; Elsevier
• Subjects: Animals; Biological and medical sciences; Cardiac electrophysiology; Cardiology. Vascular system; Cardiovascular; Cells, Cultured; Chagas Cardiomyopathy - metabolism; Chagas Cardiomyopathy - parasitology; Chagas Cardiomyopathy - pathology; Chagas' disease; Heart; Heart failure; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Human protozoal diseases; Hypertrophy; Infectious diseases; Intracellular calcium; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocarditis. Cardiomyopathies; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - parasitology; Nitric oxide; Nitric Oxide - physiology; Parasitic diseases; Phosphatidylinositol 3-Kinases - physiology; Protozoal diseases; Trypanosoma cruzi - physiology; Trypanosomiasis; Heart failure; Chagas' disease; Intracellular calcium; Nitric oxide; Cardiac electrophysiology; Hypertrophy; Heart; Protozoal disease; Calcium; Cardiomyopathy; Electrophysiology; Chagas disease; Cardiovascular disease; Inorganic element; Myocardial disease; Knowledge; Heart disease; Development; Cardiology; Trypanosomiasis; Axis; Parasitosis; Infection; Circulatory system; Intracellular
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2012.09.020

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. 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.