Macrophages Mediate Healing Properties of Fenofibrate in Experimental Chagasic Cardiomyopathy

CEVEY, AGATA CAROLINA; PIERALISI, AZUL VICTORIA; DONATO, MARTÍN; RADA, JIMENA; GELPI, JORGE RICARDO; MIRKIN, GERARDO ARIEL; GOREN, NORA BEATRIZ; PENAS, FEDERICO NICOLÁS

ACS Infectious Diseases

ACS Publications

Lugar: Washington; Año: 2023

2373-8227

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.