Fenofibrate Induces a Resolving Profile in Heart Macrophage Subsets and Attenuates Acute Chagas Myocarditis.
ACS Infect Dis
; 10(5): 1793-1807, 2024 05 10.
Article
in En
| MEDLINE
| ID: mdl-38648355
ABSTRACT
Chagas disease, caused by Trypanosoma cruzi, stands as the primary cause of dilated cardiomyopathy in the Americas. Macrophages play a crucial role in the heart's response to infection. Given their functional and phenotypic adaptability, manipulating specific macrophage subsets could be vital in aiding essential cardiovascular functions including tissue repair and defense against infection. PPARα are ligand-dependent transcription factors involved in lipid metabolism and inflammation regulation. However, the role of fenofibrate, a PPARα ligand, in the activation profile of cardiac macrophages as well as its effect on the early inflammatory and fibrotic response in the heart remains unexplored. The present study demonstrates that fenofibrate significantly reduces not only the serum activity of tissue damage biomarker enzymes (LDH and GOT) but also the circulating proportions of pro-inflammatory monocytes (CD11b+ LY6Chigh). Furthermore, both CD11b+ Ly6Clow F4/80high macrophages (MΦ) and recently differentiated CD11b+ Ly6Chigh F4/80high monocyte-derived macrophages (MdMΦ) shift toward a resolving phenotype (CD206high) in the hearts of fenofibrate-treated mice. This shift correlates with a reduction in fibrosis, inflammation, and restoration of ventricular function in the early stages of Chagas disease. These findings encourage the repositioning of fenofibrate as a potential ancillary immunotherapy adjunct to antiparasitic drugs, addressing inflammation to mitigate Chagas disease symptoms.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Fenofibrate
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Chagas Cardiomyopathy
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Macrophages
Limits:
Animals
Language:
En
Journal:
ACS Infect Dis
Year:
2024
Document type:
Article
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