In vivo pharmacological inhibition of Wnt proteins secretion during the acute phase of T. cruzi infection reduces the severity of chronic Chagas disease cardiomyopathy in BALB/c mice.

AMBROSIO, LAURA F.; ALFONSO, FERNANDO; VOLPINI, XIMENA; RIVAROLA, WALTER; MOTRAN, CLAUDIA CRISTINA; BRAJIN, AGUSTINA; FOZZATTI, LAURA

Mar del Plata

Congreso; REUNION ANUAL SAI-SAIC-SAFE; 2018

SAIC-SAI

Chagas disease is a major cause of heart disease and cardiovascular-related deaths in endemic areas located in Latin America. Each year there are approximately 12,000 deaths which are attributable to Chagas disease, typically due to severe chronic Chagas disease cardiomyopathy. Wnt signaling, essential for embryonic development, has also recently been involved in the regulation of inflammatory processes. We have previously reported that T. cruzi infection induces Wnt pathway activation and that in vivo pharmacological inhibition of the Wnt proteins secretion controls the parasite replication and improve the survival of lethally infected B6 mice. To investigate the role on Wnt proteins in determining the outcome of chronic Chagas disease, BALB/c mice were infected with 1,000 trypomastigotes of T. cruzi and treated with the inhibitor of Wnt secretion IWP-L6 (7.5 mg/kg) or vehicle (control) on days 5, 8, 11 and 14 post-infection (pi). During the acute phase of the infection, IWP-L6-treated mice showed lower levels of parasitemia (p