Beta-catenin expression is up-regulated in brachiocephalic artery and thoracic aorta before to the chronic cardiac Chagas disease development.

BRUGO, MB; MOTRAN, CC; BAIGORRI, E; CERBAN, FM; VOLPINI, XIMENA; NATALI, L; MUSRI, M

Cordoba

Workshop; The neurohumoral control of body fluis and cardiovascular homeostasis in males and females Workshop; 2019

Inst. Ferreyra

During Trypanosoma cruzi infection approximately 30% of the patients develop Chronic Chagas cardiomyopathy (CCC) characterized by myocarditis, interstitial edema, vasculitis, myocyte necrosis and early fibrosis that leads to cardiac enlargement and heart failure. We have demonstrated that upregulation of Slug, a transcription factor crucial during development, is associated with vascular remodeling and the promotion of smooth muscle cells (SMC) dedifferentiation, with TGF-β downregulating its expression on SMC and fibroblasts. Also, we have demonstrated that in infected mice the inhibition of Wnt signaling with IWP-L6 reduces the severity of CCC. Considering that, cardiovascular remodeling starts in heart and vessels during the acute phase of T. cruzi infection, and that SMC dedifferentiation and fibroblast differentiation to myofibroblasts play an important role in this process, here we tested the hypothesis that Slug is involved in both coronary vessels and heart remodeling during this infection. For that BALB/c mice were infected with 1000 T. cruzi tripomastigotes and Slug was determined in hearts by q-PCR at different days post-infection (dpi). A gradual up-regulation of Slug that was significant after 23 dpi compared to non-infected mice was observed (p=0.0277). In addition, we found that Myocd, a contractile marker of differentiated SMC, increased in heart after 18 d pi (p=0.0199) and gradually decreased while Slug began to increase. The expression of Slug remained up-regulated in heart (p=0.0330) during chronic phase of infection (180 d pi). Interestingly mice treated with IWP-L6 increased cardiac TGF-β levels, controlled Slug up-regulation and increased the number of myofibroblast in heart. Our results indicate that Slug expression in heart could be implicated in the regulation of CR during T. cruzi infection, probably by modulating both SMC and fibroblast phenotype.