The combined action of glycoinositolphospholipid from Trypanosoma cruzi and macrophage migration inhibitory factor increases proinflammatory mediator production by cardiomyocytes and vascular endothelial cells

Rigazio, Cristina S.; Mariz-Ponte, Nilo; Caballero, Eugenia Pérez; Penas, Federico Nicolás; Goren, Nora; Santamaría, Miguel H.; Corral, Ricardo S.

doi:10.1016/j.micpath.2022.105881

Cited by 1 publication

(1 citation statement)

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“…In this context, and delving further into the study of fenofibrate properties, here, we demonstrate the capability of this synthetic PPARα ligand to inhibit not only the cardiac inflammatory infiltrate but also the cardiac expression of iNOS, TNFα, IL-6, and CCR2 in the early stage of the disease. Similar results were found when the role of fenofibrate in chagasic pathogenic inflammation was studied, not only in cardiomyocytes and endothelial cell lines but also in murine primary cardiomyocytes . Additionally, these findings were consistent with an increase in resolution mediators, M2-associated mediators such as Arginase I, IL-10, PPARα, CD206, FIZZ, and YM1.…”

Section: Discussionsupporting

confidence: 86%

Fenofibrate Induces a Resolving Profile in Heart Macrophage Subsets and Attenuates Acute Chagas Myocarditis

Ruiz Luque,

Cevey,

Pieralisi

et al. 2024

ACS Infect. Dis.

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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 + LY6C high ). Furthermore, both CD11b + Ly6C low F4/80 high macrophages (MΦ) and recently differentiated CD11b + Ly6C high F4/80 high monocyte-derived macrophages (MdMΦ) shift toward a resolving phenotype (CD206 high ) 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.

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Section: Discussionsupporting

confidence: 86%