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

• Grant number: 08/06027-0
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Start date: August 01, 2008
• End date: January 31, 2009
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: João Santana da Silva
• Grantee: João Santana da Silva
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

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 forMMP-2andMMP-9were observed by day 14 after infection. Mice treated with anMMPinhibitorshowed significantly decreased heart inflammation, delayed peak in parasitemia, and improved survival rates, compared with the control group. Reduced levels of cardiac tumor necrosis factor-a,interferon-g, serum nitrite, and serum nitrate were also observed in the treated group. These results suggest an important role forMMPs in the induction of T. cruzi-induced acute myocarditis. (AU)