Trypanosoma cruzi infection induces Slug expression in heart during cardiac remodeling

VOLPINI, XIMENA; BAIGORRI, ELIANA; BRUGO, BELEN; NATALI, LAUTARO; CERBAN, FABIO; MOTRÁN, CRISTINA; MUSRI, MELINA M.

Congreso; Congreso; LXVI Reunión Anual de la Sociedad Argentina de Investigación Clínica-SAIC; 2019

Chagas disease is caused by Trypanosoma cruzi infection. Chroniccardiac manifestation (CCC) is consequence of a cardiovascularremodeling (CR) process that elicit a dilated cardiomyopathy thatcan trigger heart failure. This process starts in heart and vesselsduring the acute phase of the infection, but the molecularmechanisms are poorly understood. We reported that inhibition ofWnt proteins reduces CCC severity n BALB/c mice. Despite smoothmuscle cells (SMC) dedifferentiation and fibroblast (Fb)differentiation into myofibroblasts play an important role in CR,little is known about their contribution to this progression. Slug is atranscription factor crucial during development and pathogenesis.Our group demonstrated that Slug is associated with vascularremodeling and promotes SMC dedifferentiation. We also recentlyobserved that in vitro TGF-ß; treatment of SMC and Fb promotesSlug downregulation. In this work, we tested the hypothesis thatSlug is involved in CR process during T. cruzi infection.Consequently, we aimed to determine Slug expression in heartduring acute and chronic T. cruzi infection in absence and presenceof Wnt proteins secretion inhibition. We also evaluated thepresence of myofibroblasts in heart. BALB/c mice were infectedwith 1,000 tripomastigotes and Slug was determined in hearts byq-PCR at different days post-infection (dpi). During acute phase ofinfection, a gradual upregulation of Slug that became statisticallysignificant after 23 dpi respect to non-infected mice was observed(p= 0.0277). The expression of Slug remained upregulated in heart(p= 0.0330) during chronic phase of infection (180 dpi).Interestingly mice treated with a Wnt proteins secretion inhibitor(IWP-L6) increased TGF-ß; levels, partially blocked Slugupregulation and increased the number of myofibroblast in heart.Our results indicate that Slug could be involved in the regulation ofCR during T. cruzi infection, probably by modulating SMC and Fbphenotype.