Endogenous osteopontin induces myocardial CCL5 and MMP-2 activation that contributes to inflammation and cardiac remodeling in a mouse model of chronic Chagas heart disease

Publication date: Available online 4 October 2017 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease Author(s): Eugenia Pérez Caballero, Miguel H. Santamaría, Ricardo S. Corral Cardiac dysfunction with progressive inflammation and fibrosis is a hallmark of Chagas disease caused by persistent Trypanosoma cruzi infection. Osteopontin (OPN) is a pro-inflammatory cytokine that orchestrates mechanisms controlling cell recruitment and cardiac architecture. Our main goal was to study the role of endogenous OPN as a modulator of myocardial CCL5 chemokine and MMP-2 metalloproteinase, and its pathological impact in a murine model of Chagas heart disease. Wild-type (WT) and OPN-deficient (spp1 −/−) mice were parasite-infected (Brazil strain) for 100days. Both groups developed chronic myocarditis with similar parasite burden and survival rates. However, spp1 −/− infection showed lower heart-to-body ratio (P <0.01) as well as reduced inflammatory pathology (P <0.05), CCL5 expression (P <0.05), myocyte size (P <0.05) and fibrosis (P <0.01) in cardiac tissues. Intense OPN labeling was observed in inflammatory cells recruited to infected heart (P <0.05). Plasma concentration of MMP-2 was higher (P <0.05) in infected WT than in spp1 −/− mice. Coincidently, specific immunostaining revealed increased gelatinase expression (P <0.01) and activity (P <0.05) in the inflamed hearts from T. cruzi WT...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research