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.
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.
Gutierrez
Fredy Roberto Salazar
FR
Department of Biochemistry and Immunology, Medical School of Ribeirão Preto, University of Sao Paulo, Brazil.
Lalu
Manoj Mathew
MM
Mariano
Flávia Sammartino
FS
Milanezi
Cristiane Maria
CM
Cena
Jonathan
J
Gerlach
Raquel Fernanda
RF
Santos
Jose Eduardo Tanus
JE
Torres-Dueñas
Diego
D
Cunha
Fernando Queiróz
FQ
Schulz
Richard
R
Silva
João Santana
JS
D000818:Animals; D014355:Chagas Disease / Q000401:mortality* / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D020869:Gene Expression Profiling; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000473:pathology*; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D018512:Parasitemia; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016019:Survival Analysis; D013997:Time Factors; D014349:Trypanosoma cruzi / Q000502:physiology*
D016207:Cytokines; D009566:Nitrates; D009573:Nitrites; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9