Fenofibrate modulates inflammatory mediators as well as cross-talk between Trypanosoma cruzi- infected cardiomyocytes and fibroblasts

SEQUEYRA ALDANA; PIERALISI, AZUL VICTORIA; ÁGATA CAROLINA CEVEY; GERARDO ARIEL MIRKIN; GOREN, NORA; FEDERICO N PENAS

Ciudad autónoma de Buenos Aires

Congreso; Reunión de Sociedades de Biociencias 2021; 2021

Sociedad Argentina de Investigación Clínica (SAIC)

Chronic chagasic cardiomyopathy is characterized by parasite persistence, chronic inflammation and cardiac cell (Mc) death that may end lead to fbrosis and cardiac insuffciency. Activated fbroblasts (Fb) are involved in this process. Previous results from our group show that fenonofbrate (Fen), a PPARalpha ligand, modulates the expression of inflammatory mediators, prevents fbrosis and restores cardiac function in Trypanosoma cruzi (Tc) -infected mice. To deepen into the knowledge of the role of Mc and Fb in these events, in the present work we used an in vitro model of neonatal murine cardiac cells. We studied the modulator role of Fen on the inflammatory response of Mc and Fb infected with Tc. Mc and Fb were characterized by the expression of troponin C and s alpha-SMA, respectively, using Western blot (Wb). Wb and RT-qPCR analysis showed that Tc stimulated the expression of pro-inflammatory and pro-fbrotic enzymes like NOS2 and MMP-9 in Mc and Fb, whereas treatment with Fen (100µM) inhibited such expression in both cell lineages. In addition, after 48 h of infection we observed increased expression of CTGF, MMP-2 and TGF-beta by RT-qPCR in Mc and Fb, whereas Fen inhibited such increment (p