Implication of transforming growth factor- beta 1 in chagas disease myocardiopathy

Cardiac dysfunction with progressive fibrosis is a hallmark of Chagas disease. To evaluate the involvement of transforming growth factor (TGF)- beta 1 in this disease, TGF- beta 1 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- beta 1 than did healthy persons, and 27% of patients in the Card 1 group had higher TGF- beta 1 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- beta 1 signaling pathway) in cell nuclei. The higher levels of latent TGF- beta 1 observed in patients with myocardiopathy, together with intracellular activation of the TGF- beta 1 pathway and tissue fibrosis, suggest that TGF- beta 1 plays an important role in Chagas disease. TGF- beta 1 may represent a new target for preventive and curative treatments of Chagas disease.