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Macrophages Mediate Healing Properties of Fenofibrate in Experimental Chagasic Cardiomyopathy
Ágata Carolina Cevey1, Azul Victoria Pieralisi1, Martín Donato2
1Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS). Facultad de Medicina, CONICET - Universidad de Buenos Aires, Buenos Aires C1121ABG, Argentina.
Insights
Fenofibrate treatment modulates macrophage-mediated inflammation and fibrosis in chronic Chagas disease cardiomyopathy. Macrophages are essential for fenofibrate
Area of Science:
- Immunology
- Cardiology
- Parasitology
Background:
- Chronic cardiomyopathy is a major outcome of Chagas disease, driven by parasite persistence and inflammation.
- Fenofibrate, a PPAR-α ligand, regulates inflammatory responses, but its role in Chagas disease cardiomyopathy involving macrophages is unknown.
Purpose of the Study:
- To investigate the role of macrophages in fenofibrate's effects on Chagas disease-induced heart inflammation and fibrosis.
- To determine if macrophages are necessary for fenofibrate to restore cardiac function.
Main Methods:
- Experimental infection of mice with *Trypanosoma cruzi*
- Treatment with fenofibrate
- Macrophage depletion studies
- Analysis of cardiac inflammation, fibrosis, and ventricular function
Main Results:
- Macrophages are critical for fenofibrate's ability to reduce heart inflammation and fibrosis in *Trypanosoma cruzi*-infected mice.
- Fenofibrate requires macrophages to improve cardiac ventricular function loss.
- Improved cardiac function correlates with an anti-inflammatory microenvironment.
Conclusions:
- Macrophages play a fundamental role in fenofibrate's therapeutic effects against Chagas disease cardiomyopathy.
- Fenofibrate's potential as a treatment for chronic Chagas disease is supported by its macrophage-dependent actions.
- Targeting macrophages could be a strategy to manage Chagas disease complications.
Abstract:
Chronic cardiomyopathy is one of the most relevant outcomes of Chagas disease associated with parasite persistence and exacerbated inflammatory response. Fenofibrate, a third generation fibric acid derivative and peroxisome proliferator-activated receptor-α ligand, is involved in the regulation of inflammatory response. However, the participation of macrophages in this scenario has not been elucidated. Here we show, for the first time, that macrophages play a fundamental role in the fenofibrate-mediated modulation of heart pro-inflammatory response and fibrosis caused by the infection with Trypanosoma cruzi. Furthermore, macrophages are required for fenofibrate to improve the loss of ventricular function and this restoration correlates with an anti-inflammatory microenvironment. Understanding the contributions of macrophages to the healing properties of fenofibrate reinforces its potential use as a therapeutic drug, with the aim of helping to solve a public health problem, such as chronic Chagas disease.
