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

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1468-1476
Number of pages9
JournalJournal of Infectious Diseases
Volume197
Issue number10
DOIs
StatePublished - 15 May 2008
Externally publishedYes

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this