TRYPANOSOMA CRUZI INFECTION INDUCES SLUG EXPRESSION IN HEART DURING CARDIAC REMODELING

VOLPINI, XIMENA; BAIGORRI, RUTH ELIANA; BRUGO, MARÍA BELÉN; NATALI, LAUTARO; CERBAN, FABIO MARCELO; MOTRÁN, CRISTINA; MUSRI, MELINA

Mar del Plata

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2019

Chagas disease is caused by Trypanosomacruzi infection. Chronic cardiac manifestation (CCC) isconsequence of a cardiovascular remodeling (CR) process thatelicit a dilated cardiomyopathy that can trigger heart failure. Thisprocess starts in heart and vessels during the acute phase of theinfection, but the molecular mechanisms are poorly understood.We reported that inhibition of Wnt proteins reduces CCC severityn BALB/c mice. Despite smooth muscle cells (SMC)dedifferentiation and fibroblast (Fb) differentiation intomyofibroblasts play an important role in CR, little is known abouttheir contribution to this progression. Slug is a transcriptionfactor crucial during development and pathogenesis. Our groupdemonstrated that Slug is associated with vascular remodelingand promotes SMC dedifferentiation. We also recently observedthat in vitro TGF-ß; treatment of SMC and Fb promotes Slugdownregulation. In this work, we tested the hypothesis that Slugis involved in CR process during T. cruzi infection. Consequently,we aimed to determine Slug expression in heart during acute andchronic T. cruzi infection in absence and presence of Wntproteins secretion inhibition. We also evaluated the presence ofmyofibroblasts in heart. BALB/c mice were infected with 1,000tripomastigotes and Slug was determined in hearts by q-PCR atdifferent days post-infection (dpi). During acute phase ofinfection, a gradual upregulation of Slug that became statisticallysignificant after 23 dpi respect to non-infected mice wasobserved (p= 0.0277). The expression of Slug remainedupregulated in heart (p= 0.0330) during chronic phase ofinfection (180 dpi). Interestingly mice treated with a Wntproteins secretion inhibitor (IWP-L6) increased TGF-ß; levels,partially blocked Slug upregulation and increased the number ofmyofibroblast in heart. Our results indicate that Slug could beinvolved in the regulation of CR during T. cruzi infection,probably by modulating SMC and Fb phenotype.