title: Matrix metalloproteinases 2 and 9 are differentially expressed in patients with indeterminate and cardiac clinical forms of Chagas disease.
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.
authors.affiliation: Centro de Pesquisas René Rachou-FIOCRUZ, Belo Horizonte/MG, Brazil.
authors.forename: Rafaelle Christine Gomes
authors.initials: RC
authors.lastname: Fares
authors.forename: Juliana de Assis Silva
authors.initials: Jde A
authors.lastname: Gomes
authors.forename: Luciana Ribeiro
authors.initials: LR
authors.lastname: Garzoni
authors.forename: Mariana Caldas
authors.initials: MC
authors.lastname: Waghabi
authors.forename: Roberto Magalhães
authors.initials: RM
authors.lastname: Saraiva
authors.forename: Nayara Ingrid
authors.initials: NI
authors.lastname: Medeiros
authors.forename: Roberta
authors.initials: R
authors.lastname: Oliveira-Prado
authors.forename: Luiz Henrique Conde
authors.initials: LH
authors.lastname: Sangenis
authors.forename: Mayara da Costa
authors.initials: Mda C
authors.lastname: Chambela
authors.forename: Fernanda Fortes
authors.initials: FF
authors.lastname: de Araújo
authors.forename: Andréa
authors.initials: A
authors.lastname: Teixeira-Carvalho
authors.forename: Marcos Paulo
authors.initials: MP
authors.lastname: Damásio
authors.forename: Vanessa Azevedo
authors.initials: VA
authors.lastname: Valente
authors.forename: Karine Silvestre
authors.initials: KS
authors.lastname: Ferreira
authors.forename: Giovane Rodrigo
authors.initials: GR
authors.lastname: Sousa
authors.forename: Manoel Otávio da Costa
authors.initials: MO
authors.lastname: Rocha
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Correa-Oliveira
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002598:Chagas Cardiomyopathy / Q000201:enzymology* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged
chemical_list: D015415:Biomarkers; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9