Novel insights into the development of chagasic cardiomyopathy: Role of PI3Kinase/NO axis
| Autor: | Enéas Ricardo de Morais Gomes, Jader S. Cruz, Paula Peixoto Campos, Silvia Guatimosim, Policarpo Sales-Junior, Hugo L. Duarte, Ricardo T. Gazzinelli, Anderson A. Ferreira, Catherine Ropert, Nazareth N. Rocha, Rodrigo R. Resende, Aline Lara, Danilo Roman-Campos |
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| Rok vydání: | 2013 |
| Předmět: |
Chagas Cardiomyopathy
Chagas disease medicine.medical_specialty Trypanosoma cruzi Cardiac electrophysiology Cardiomyopathy Heart failure Disease Contractility Mice Phosphatidylinositol 3-Kinases Internal medicine medicine Animals Myocyte Myocytes Cardiac Intracellular calcium Cells Cultured PI3K/AKT/mTOR pathway Mice Knockout business.industry Nitric oxide Hypertrophy medicine.disease Mice Inbred C57BL Chagas' disease Cardiology business Cardiology and Cardiovascular Medicine |
| Zdroj: | International Journal of Cardiology. 167(6):3011-3020 |
| ISSN: | 0167-5273 |
| DOI: | 10.1016/j.ijcard.2012.09.020 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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