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Matrix Metalloproteinases 2 and 9 Are Differentially Expressed in Patients with Indeterminate and Cardiac Clinical Forms of Chagas Disease

2013; American Society for Microbiology; Volume: 81; Issue: 10 Linguagem: Inglês

10.1128/iai.00153-13

1098-5522

Rafaelle Fares‐Gusmao, Juliana de Assis Silva Gomes, Luciana Ribeiro Garzoni, Mariana Caldas Waghabi, Roberto Magalhães Saraiva, Nayara I. Medeiros, Rodrigo Cardoso de Oliveira, Luiz Henrique Conde Sangenis, Mayara da Costa Chambela, Fernanda Fortes de Araújo, Andréa Teixeira‐Carvalho, Marcos Damasio, Vanessa Azevedo Valente, Karine Silvestre Ferreira, Giovane Rodrigo Sousa, Manoel Otávio da Costa Rocha, Rodrigo Corrêa‐Oliveira,

Studies on Chitinases and Chitosanases

ABSTRACT Dilated chronic cardiomyopathy (DCC) from Chagas disease is associated with myocardial remodeling and interstitial fibrosis, resulting in extracellular matrix (ECM) changes. In this study, we characterized for the first time the serum matrix metalloproteinase 2 (MMP-2) and MMP-9 levels, as well as their main cell sources in peripheral blood mononuclear cells from patients presenting with the indeterminate (IND) or cardiac (CARD) clinical form of Chagas disease. Our results showed that serum levels of MMP-9 are associated with the severity of Chagas disease. The analysis of MMP production by T lymphocytes showed that CD8 + T cells are the main mononuclear leukocyte source of both MMP-2 and MMP-9 molecules. Using a new 3-dimensional model of fibrosis, we observed that sera from patients with Chagas disease induced an increase in the extracellular matrix components in cardiac spheroids. Furthermore, MMP-2 and MMP-9 showed different correlations with matrix proteins and inflammatory cytokines in patients with Chagas disease. Our results suggest that MMP-2 and MMP-9 show distinct activities in Chagas disease pathogenesis. While MMP-9 seems to be involved in the inflammation and cardiac remodeling of Chagas disease, MMP-2 does not correlate with inflammatory molecules.