1. Association of Cardiac Galectin-3 Expression, Myocarditis, and Fibrosis in Chronic Chagas Disease Cardiomyopathy.
- Author
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Souza BSF, Silva DN, Carvalho RH, Sampaio GLA, Paredes BD, Aragão França L, Azevedo CM, Vasconcelos JF, Meira CS, Neto PC, Macambira SG, da Silva KN, Allahdadi KJ, Tavora F, de Souza Neto JD, Dos Santos RR, and Soares MBP
- Subjects
- Acetylgalactosamine pharmacology, Animals, Cell Proliferation physiology, Cell Survival physiology, Chronic Disease, Collagen Type I biosynthesis, Fibrosis etiology, Fibrosis metabolism, Galectin 3 antagonists & inhibitors, Heart Transplantation, Humans, Macrophages metabolism, Mice, Mice, Inbred C57BL, Myocarditis etiology, Myocardium metabolism, Myofibroblasts metabolism, T-Lymphocytes metabolism, Chagas Cardiomyopathy metabolism, Galectin 3 metabolism, Myocarditis metabolism, Myocardium pathology
- Abstract
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.)
- Published
- 2017
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