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Rapamycin Treatment Reduces Acute Myocarditis Induced by Trypanosoma cruzi Infection
Thabata L A Duque1,2, Cynthia M Cascabulho2, Gabriel M Oliveira1
1Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil.
Insights
Rapamycin treatment reduced Chagasic cardiomyopathy and inflammation by activating autophagy (a cellular process). This study shows autophagy induction can protect the heart from parasite-induced damage, despite not affecting the parasite itself.
Area of Science:
- Cardiology
- Parasitology
- Immunology
Background:
- Chagas disease, caused by Trypanosoma cruzi, leads to Chagasic cardiomyopathy, a major cause of mortality.
- Cardiac dysfunction in Chagas disease results from tissue remodeling, fibrosis, and inflammation.
- Autophagy is a cellular pathway with potential cardioprotective roles.
Purpose of the Study:
- To investigate if in vivo activation of autophagy by rapamycin can mitigate parasite-induced myocarditis in Chagas disease.
- To assess the impact of autophagy induction on cardiac function, inflammation, and parasite load.
Main Methods:
- Mice infected with Trypanosoma cruzi were treated with rapamycin, an autophagy inducer.
- Cardiac tissue and blood were analyzed for autophagy markers (LC3), inflammation, cardiac damage, and parasite presence.
- Electrical cardiac function and parasitemia were monitored.
Main Results:
- Rapamycin treatment upregulated the autophagy marker LC3 in cardiac tissue.
- Infected mice treated with rapamycin exhibited reduced myocarditis, cardiac damage, and pro-inflammatory cytokine production.
- Electrical cardiac dysfunctions were also decreased in rapamycin-treated mice.
- However, rapamycin did not affect the parasite's life cycle or parasitemia.
Conclusions:
- Autophagy induction by rapamycin partially controls cardiac inflammation in Chagas disease.
- Autophagy activation demonstrates cardioprotective effects against Trypanosoma cruzi-induced myocarditis.
- The findings highlight the complex interplay of cellular pathways in Chagas disease pathogenesis.
Abstract:
Chagas disease affects millions of people mainly in Latin America and is a protozoan illness caused by the parasite Trypanosoma cruzi. Chagasic cardiomyopathy is the leading cause of mortality of infected patients, due to compromised electrical and mechanical cardiac function induced by tissue remodeling, especially fibrosis, and lymphocytic infiltration. Some cellular biochemical pathways can be protective to the heart, and we tested if the in vivo activation of the autophagic machinery by rapamycin could reduce parasite-induced myocarditis. Regarding the expression of LC3, an autophagy marker, we observed its upregulation in the cardiac tissue of infected untreated mice. However, after rapamycin treatment, an autophagy inducer, infected mice showed reduced electrical cardiac dysfunctions, myocarditis, cardiac damage, and reduced production of pro-inflammatory cytokines by the heart. On the other hand, the parasite's life cycle was not affected, and we observed no modulations in cardiac tissue or blood parasitemia. Our data indicate that, at least partially, autophagy induction controls inflammation in the heart¸ illustrating the complexity of the pathways that concur to the development of the infection.
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