Corral, Ricardo SGuerrero, Néstor ACuervo, HenarGironès, NúriaFresno, Manuel2024-01-172024-01-172013PLoS Negl Trop Dis. 2013;7(2):e2034.http://hdl.handle.net/20.500.12105/17198Trypanosoma cruzi, the causative agent of Chagas' disease, induces multiple responses in the heart, a critical organ of infection and pathology in the host. Among diverse factors, eicosanoids and the vasoactive peptide endothelin-1 (ET-1) have been implicated in the pathogenesis of chronic chagasic cardiomyopathy. In the present study, we found that T. cruzi infection in mice induces myocardial gene expression of cyclooxygenase-2 (Cox2) and thromboxane synthase (Tbxas1) as well as endothelin-1 (Edn1) and atrial natriuretic peptide (Nppa). T. cruzi infection and ET-1 cooperatively activated the Ca(2+)/calcineurin (Cn)/nuclear factor of activated T cells (NFAT) signaling pathway in atrial myocytes, leading to COX-2 protein expression and increased eicosanoid (prostaglandins E(2) and F(2α), thromboxane A(2)) release. Moreover, T. cruzi infection of ET-1-stimulated cardiomyocytes resulted in significantly enhanced production of atrial natriuretic peptide (ANP), a prognostic marker for impairment in cardiac function of chagasic patients. Our findings support an important role for the Ca(2+)/Cn/NFAT cascade in T. cruzi-mediated myocardial production of inflammatory mediators and may help define novel therapeutic targets.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/AnimalsAtrial Natriuretic FactorCalcineurinCalciumCyclooxygenase 2Endothelin-1Gene Expression ProfilingInflammationMiceMice, Inbred BALB CMice, Inbred C57BLMonocytesMyocytes, CardiacNFATC Transcription FactorsNatriuretic Peptide, C-TypeProtein PrecursorsSignal TransductionThromboxane-A SynthaseTrypanosoma cruziAttribution-NonCommercial-NoDerivatives 4.0 Internacional2340919972e203410.1371/journal.pntd.00020341935-2735PLoS neglected tropical diseasesopen access