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Granulocyte colony-stimulating factor treatment in chronic Chagas disease: preservation and improvement of cardiac
Simone G Macambira1, Juliana F Vasconcelos, Claudio R S Costa
1Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil.
Insights
Granulocyte colony-stimulating factor (G-CSF) therapy improved cardiac function and reduced inflammation in experimental Chagasic cardiomyopathy. This G-CSF treatment offers a potential therapeutic strategy for heart failure in Chagas disease.
Area of Science:
- Cardiology
- Immunology
- Parasitology
Background:
- Chagas disease causes heart failure, particularly in Latin America.
- Current treatments for Chagasic cardiomyopathy are limited, often requiring cardiac transplantation.
- Experimental models are crucial for developing new therapeutic strategies.
Purpose of the Study:
- To investigate the therapeutic effects of granulocyte colony-stimulating factor (G-CSF) on experimental chronic chagasic cardiomyopathy.
- To evaluate the impact of G-CSF on cardiac function, inflammation, fibrosis, and parasite load.
Main Methods:
- C57BL/6 mice were infected with Trypanosoma cruzi to induce chronic chagasic cardiomyopathy.
- Mice received either G-CSF or saline (control) treatment.
- Functional, immunological, and histopathological evaluations were performed post-treatment.
Main Results:
- G-CSF treatment reduced cardiac inflammation and fibrosis compared to controls.
- G-CSF did not alter parasite load but increased apoptotic inflammatory cells in the heart.
- Cardiac function improved or stabilized with G-CSF, while controls deteriorated.
- Exercise performance (treadmill distance, time, VO(2), VCO(2), RER) significantly improved in G-CSF treated mice.
Conclusions:
- G-CSF demonstrates beneficial effects on cardiac structure and function in experimental chagasic cardiomyopathy.
- G-CSF treatment correlates with improved whole-animal performance and cardiac health.
- G-CSF represents a promising therapeutic avenue for managing Chagas disease-related heart failure.
Abstract:
This study investigates the effects of granulocyte colony-stimulating factor (G-CSF) therapy in experimental chronic chagasic cardiomyopathy. Chagas disease is one of the leading causes of heart failure in Latin America and remains without an effective treatment other than cardiac transplantation. C57BL/6 mice were infected with 10(3) trypomastigotes of Trypanosoma cruzi, and chronic chagasic mice were treated with G-CSF or saline (control). Evaluations following treatment were functional, immunological, and histopathological. Comparing hearts of G-CSF-treated mice showed reduced inflammation and fibrosis compared to saline-treated chagasic mice. G-CSF treatment did not alter the parasite load but caused an increase in the number of apoptotic inflammatory cells in the heart. Cardiac conductance disturbances in all infected animals improved or remained stable due to the G-CSF treatment, whereas all of the saline-treated mice deteriorated. The distance run on a treadmill and the exercise time were significantly greater in G-CSF-treated mice when compared to chagasic controls, as well as oxygen consumption (VO(2)), carbon dioxide production (VCO(2)), and respiratory exchange ration (RER) during exercise. Administration of G-CSF in experimental cardiac ischemia had beneficial effects on cardiac structure, which were well correlated with improvements in cardiac function and whole animal performance.
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