Author:
Fares Rafaelle Christine Gomes,Gomes Juliana de Assis Silva,Garzoni Luciana Ribeiro,Waghabi Mariana Caldas,Saraiva Roberto Magalhães,Medeiros Nayara Ingrid,Oliveira-Prado Roberta,Sangenis Luiz Henrique Conde,Chambela Mayara da Costa,de Araújo Fernanda Fortes,Teixeira-Carvalho Andréa,Damásio Marcos Paulo,Valente Vanessa Azevedo,Ferreira Karine Silvestre,Sousa Giovane Rodrigo,Rocha Manoel Otávio da Costa,Correa-Oliveira Rodrigo
Abstract
ABSTRACTDilated 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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
47 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献