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Implication of transforming growth factor-beta1 in Chagas disease myocardiopathy
Tania C Araújo-Jorge1, Mariana C Waghabi, Alejandro M Hasslocher-Moreno
1Laboratory of Cell Biology, Department of Ultrastructure and Cell Biology, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. taniaaj@ioc.fiocruz.br
Insights
Transforming growth factor-beta1 (TGF-beta1) is elevated in Chagas disease patients, correlating with cardiac dysfunction and fibrosis. This suggests TGF-beta1 is a potential therapeutic target for Chagas disease treatment.
Area of Science:
- Cardiology
- Immunology
- Parasitology
Background:
- Chagas disease is characterized by cardiac dysfunction and fibrosis.
- The role of transforming growth factor-beta1 (TGF-beta1) in Chagas disease pathogenesis is not fully understood.
Purpose of the Study:
- To evaluate the involvement of TGF-beta1 in Chagas disease.
- To assess TGF-beta1 levels across different disease stages.
- To investigate the TGF-beta1 signaling pathway in cardiac tissue.
Main Methods:
- Measured circulating TGF-beta1 levels in patients at indeterminate (IND), cardiac (Card 1), and advanced cardiac (Card 2) stages.
- Performed immunohistochemical analysis of cardiac biopsy specimens.
- Assessed fibronectin and phosphorylated Smad 2 (pSmad2) expression.
Main Results:
- All Chagas disease patients exhibited higher TGF-beta1 levels than healthy controls.
- Elevated TGF-beta1 levels were observed in Card 1 patients compared to IND patients.
- Cardiac biopsies showed increased fibronectin and nuclear pSmad2, indicating extracellular matrix deposition and TGF-beta1 pathway activation.
Conclusions:
- Elevated TGF-beta1 levels and activated TGF-beta1 signaling are associated with cardiac fibrosis in Chagas disease.
- TGF-beta1 plays a significant role in the progression of Chagas disease cardiomyopathy.
- TGF-beta1 represents a potential therapeutic target for Chagas disease.
Abstract:
Cardiac dysfunction with progressive fibrosis is a hallmark of Chagas disease. To evaluate the involvement of transforming growth factor (TGF)-beta1 in this disease, TGF-beta1 levels in patients were measured at 3 stages: asymptomatic indeterminate (IND), cardiac with no or slight heart dysfunction (Card 1), and cardiac with moderate or severe heart dysfunction (Card 2). All patients had significantly higher circulating levels of TGF-beta1 than did healthy persons, and 27% of patients in the Card 1 group had higher TGF-beta1 levels than did patients in the IND group. Immunohistochemical analysis of cardiac biopsy specimens showed strong fibronectin staining in the extracellular matrix and staining for phosphorylated Smad 2 (activation of the TGF-beta1 signaling pathway) in cell nuclei. The higher levels of latent TGF-beta1 observed in patients with myocardiopathy, together with intracellular activation of the TGF-beta1 pathway and tissue fibrosis, suggest that TGF-beta1 plays an important role in Chagas disease. TGF-beta1 may represent a new target for preventive and curative treatments of Chagas disease.