Implication of transforming growth factor-beta1 in Chagas disease myocardiopathy.
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.
Araújo-Jorge
Tania C
TC
Laboratory of Cell Biology, Department of Ultrastructure and Cell Biology, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. taniaaj@ioc.fiocruz.br
Waghabi
Mariana C
MC
Hasslocher-Moreno
Alejandro M
AM
Xavier
Sérgio S
SS
Higuchi
Maria de Lourdes
Mde L
Keramidas
Michelle
M
Bailly
Sabine
S
Feige
Jean-Jacques
JJ
D000328:Adult; D000368:Aged; D001706:Biopsy; D002598:Chagas Cardiomyopathy / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000032:analysis / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D051899:Smad2 Protein; D015534:Trans-Activators / Q000032:analysis / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000097:blood*; D053773:Transforming Growth Factor beta1
D004268:DNA-Binding Proteins; D005353:Fibronectins; C497782:SMAD2 protein, human; D051899:Smad2 Protein; C508960:TGFB1 protein, human; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1