Association of Cardiac Galectin-3 Expression, Myocarditis, and Fibrosis in Chronic Chagas Disease Cardiomyopathy.
Chronic Chagas disease cardiomyopathy, caused by Trypanosoma cruzi infection, is a major cause of heart failure in Latin America. Galectin-3 (Gal-3) has been linked to cardiac remodeling and poor prognosis in heart failure of different etiologies. Herein, we investigated the involvement of Gal-3 in the disease pathogenesis and its role as a target for disease intervention. Gal-3 expression in mouse hearts was evaluated during T. cruzi infection by confocal microscopy and flow cytometry analysis, showing a high expression in macrophages, T cells, and fibroblasts. In vitro studies using Gal-3 knockdown in cardiac fibroblasts demonstrated that Gal-3 regulates cell survival, proliferation, and type I collagen synthesis. In vivo blockade of Gal-3 with N-acetyl-d-lactosamine in T. cruzi-infected mice led to a significant reduction of cardiac fibrosis and inflammation in the heart. Moreover, a modulation in the expression of proinflammatory genes in the heart was observed. Finally, histological analysis in human heart samples obtained from subjects with Chagas disease who underwent heart transplantation showed the expression of Gal-3 in areas of inflammation, similar to the mouse model. Our results indicate that Gal-3 plays a role in the pathogenesis of experimental chronic Chagas disease, favoring inflammation and fibrogenesis. Moreover, by demonstrating Gal-3 expression in human hearts, our finding reinforces that this protein could be a novel target for drug development for Chagas cardiomyopathy.
Gonçalo Moniz Research Center, Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Brazil; Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil.
Bruno Solano de Freitas
BSF
Souza
Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil.
Daniela Nascimento
DN
Silva
Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil.
Rejane Hughes
RH
Carvalho
Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil.
Gabriela Louise de Almeida
GLA
Sampaio
Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil.
Bruno Diaz
BD
Paredes
Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil.
Luciana
L
Aragão França
Gonçalo Moniz Research Center, Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Brazil; Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil.
Carine Machado
CM
Azevedo
Gonçalo Moniz Research Center, Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Brazil; Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil.
Juliana Fraga
JF
Vasconcelos
Gonçalo Moniz Research Center, Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Brazil; Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil.
Cassio Santana
CS
Meira
Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil.
Paulo Chenaud
PC
Neto
Gonçalo Moniz Research Center, Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Brazil; Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil; Health Sciences Institute, Federal University of Bahia, Salvador, Brazil.
Simone Garcia
SG
Macambira
Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil.
Kátia Nunes
KN
da Silva
Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil.
Kyan James
KJ
Allahdadi
Messejana Heart and Lung Hospital, Fortaleza, Brazil.
Fabio
F
Tavora
Messejana Heart and Lung Hospital, Fortaleza, Brazil.
João David
JD
de Souza Neto
Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil.
Ricardo Ribeiro
RR
Dos Santos
Gonçalo Moniz Research Center, Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Brazil; Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil. Electronic address: milena@bahia.fiocruz.br.
Milena Botelho Pereira
MBP
Soares
D000116:Acetylgalactosamine / Q000494:pharmacology; D000818:Animals; D049109:Cell Proliferation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002598:Chagas Cardiomyopathy / Q000378:metabolism*; D002908:Chronic Disease; D024042:Collagen Type I / Q000096:biosynthesis; D005355:Fibrosis / Q000209:etiology / Q000378:metabolism; D037502:Galectin 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016027:Heart Transplantation; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009205:Myocarditis / Q000209:etiology / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D058628:Myofibroblasts / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism
D024042:Collagen Type I; D037502:Galectin 3; D000116:Acetylgalactosamine