Increased Activities of Cardiac Matrix Metalloproteinases Matrix Metalloproteinase (MMP)–2 and MMP‐9 Are Associated with Mortality during the Acute Phase of ExperimentalTrypanosoma cruziInfection
Author(s) -
Fredy R. S. Gutierrez,
Manoj M. Lalu,
Flávia S. Mariano,
Cristiane M. Milanezi,
Jonathan Cena,
Raquel F. Gerlach,
José Eduardo Tanus dos Santos,
Diego TorresDueñas,
Fernando Q. Cunha,
Richard Schulz,
João S. Silva
Publication year - 2008
Publication title -
the journal of infectious diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.69
H-Index - 252
eISSN - 1537-6613
pISSN - 0022-1899
DOI - 10.1086/587487
Subject(s) - matrix metalloproteinase , trypanosoma cruzi , parasitemia , inflammation , myocarditis , chagas disease , zymography , immunology , tumor necrosis factor alpha , matrix metalloproteinase inhibitor , chemokine , biology , medicine , parasite hosting , plasmodium falciparum , world wide web , computer science , malaria
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-alpha, interferon-gamma, 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.
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