Increased activities of cardiac matrix metalloproteinases matrix metalloproteinase (MMP)-2 and MMP-9 are associated with mortality during the acute phase of experimental Trypanosoma cruzi infection

Fredy Roberto Salazar Gutierrez, Manoj Mathew Lalu, Flávia Sammartino Mariano, Cristiane Maria Milanezi, Jonathan Cena, Raquel Fernanda Gerlach, Jose Eduardo Tanus Santos, Diego Torres-Dueñas, Fernando Queiróz Cunha, Richard Schulz, João Santana Silva

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81 Citas (Scopus)

Resumen

The strong inflammatory reaction that occurs in the heart during the acute phase of Trypanosoma cruzi infection is modulated by cytokines and chemokines produced by leukocytes and cardiomyocytes. Matrix metalloproteinases (MMPs) have recently emerged as modulators of cardiovascular inflammation. In the present study we investigated the role of MMP-2 and MMP-9 in T. cruzi-induced myocarditis, by use of immunohistochemical analysis, gelatin zymography, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction to analyze the cardiac tissues of T. cruzi-infected C57BL/6 mice. Increased transcripts levels, immunoreactivity, and enzymatic activity for MMP-2 and MMP-9 were observed by day 14 after infection. Mice treated with an MMP inhibitor showed significantly decreased heart inflammation, delayed peak in parasitemia, and improved survival rates, compared with the control group. Reduced levels of cardiac tumor necrosis factor-α, interferon-γ, serum nitrite, and serum nitrate were also observed in the treated group. These results suggest an important role for MMPs in the induction of T. cruzi-induced acute myocarditis.

Idioma originalInglés
Páginas (desde-hasta)1468-1476
Número de páginas9
PublicaciónJournal of Infectious Diseases
Volumen197
N.º10
DOI
EstadoPublicada - 15 may. 2008
Publicado de forma externa

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