Association of Cardiac Galectin-3 Expression, Myocarditis, and Fibrosis in Chronic Chagas Disease Cardiomyopathy.

Autor:	Souza BSF; Gonçalo Moniz Research Center, Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Brazil; Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil., Silva DN; Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil., Carvalho RH; Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil., Sampaio GLA; Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil., Paredes BD; Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil., Aragão França L; Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil., Azevedo CM; Gonçalo Moniz Research Center, Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Brazil; Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil., Vasconcelos JF; Gonçalo Moniz Research Center, Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Brazil; Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil., Meira CS; Gonçalo Moniz Research Center, Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Brazil; Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil., Neto PC; Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil., Macambira SG; 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., da Silva KN; Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil., Allahdadi KJ; Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil., Tavora F; Messejana Heart and Lung Hospital, Fortaleza, Brazil., de Souza Neto JD; Messejana Heart and Lung Hospital, Fortaleza, Brazil., Dos Santos RR; Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil., Soares MBP; 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.
Jazyk:	angličtina
Zdroj:	The American journal of pathology [Am J Pathol] 2017 May; Vol. 187 (5), pp. 1134-1146. Date of Electronic Publication: 2017 Mar 17.
DOI:	10.1016/j.ajpath.2017.01.016
Abstrakt:	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. (Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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