AOKI MARIA DEL PILAR
Congresos y reuniones científicas
Título:
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.
Autor/es:
VOLPINI, X; AMBROSIO, L; BRAJÍN, A; AOKI, MP; RIVAROLA, G; ALFONSO, F; FOSSATTI, L; MOTRAN, C
Reunión:
Exposición; REUNION ANUAL DE A SOCIEDAD ARGENTINA DE INMUNOLOGIA; 2018
Resumen:
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 pathways 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<0.05), associated with increased serum levels of IL-
12 (p<0.05) and TNF (p<0.001) and decreased function
of Treg cells (p<0.05) compared with control mice. At the
chronic phase of the infection (180 days pi), the cardiac
electrophysiology and global left ventricular function (LV)
were studied by electrocardiogram (ECG) and 2D-echocardiogram
(ECHO), respectively. The ECGs of IWP-L6-
treated mice were improved compared with control mice,
because non-treated group presented a significant prolongation
in the QT intervals (p<0.001), suggesting intraventricular
conduction blockages; meanwhile, this abnormality
was not observed in the IWP-L6-treated group.
In addition, ECHO revealed systolic disfunction that was
only present in control mice (p<0.01). Our results indicate
that the inhibition of Wnt proteins secretion during
the acute phase of the infection might controls parasite
replication, thus preventing the development of chronic
cardiomyopathy.
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 pathways 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<0.05), associated with increased serum levels of IL-
12 (p<0.05) and TNF (p<0.001) and decreased function
of Treg cells (p<0.05) compared with control mice. At the
chronic phase of the infection (180 days pi), the cardiac
electrophysiology and global left ventricular function (LV)
were studied by electrocardiogram (ECG) and 2D-echocardiogram
(ECHO), respectively. The ECGs of IWP-L6-
treated mice were improved compared with control mice,
because non-treated group presented a significant prolongation
in the QT intervals (p<0.001), suggesting intraventricular
conduction blockages; meanwhile, this abnormality
was not observed in the IWP-L6-treated group.
In addition, ECHO revealed systolic disfunction that was
only present in control mice (p<0.01). Our results indicate
that the inhibition of Wnt proteins secretion during
the acute phase of the infection might controls parasite
replication, thus preventing the development of chronic
cardiomyopathy.
