Carvedilol treatment (10 M for 72 h) of T. cruzi-infected 3D cardiac spheroids recovered cell viability and significantly reduced fibronectin expression, demonstrating antifibrotic potential.
Does carvedilol reduce fibrosis and improve cell viability in a 3D cardiac spheroid/organoid model infected with Trypanosoma cruzi?
Carvedilol demonstrates antifibrotic potential and improves cell viability in a 3D cardiac spheroid model of Trypanosoma cruzi infection, suggesting possible therapeutic relevance for Chagasic cardiomyopathy.
Introduction: Chronic chagasic cardiomyopathy (CCC) represents one of the main complications of Chagas disease (CD) and is characterized by cardiac hypertrophy and progressive fibrosis, leading to electrical and contractile dysfunction of the heart.Therapeutic strategies targeting fibrosis remain limited.Carvedilol (carv) is a -blocker with vasodilatory, anti-inflammatory, antioxidant, and cardioprotective properties, widely used in hypertension and heart failure (HF), including symptoms of CCC; however, its impact on fibrosis in CD has not yet been elucidated.Objectives: Our group developed a three-dimensional (3D) model of cardiac spheroids/organoids that reproduces fibrosis and hypertrophy induced by Trypanosoma cruzi (T.cruzi) infection, mimicking tissue architecture and the in vivo microenvironment, providing a tool for testing antifibrotic drugs.Using this model, we evaluated the effects of carv on extracellular matrix (ECM) modulation and on T. cruzi cell infection.Methodology: Primary cardiac cells from mouse fetuses were isolated and characterized by staining (panoptic) and immunofluorescence for troponin T. Carv cytotoxicity was tested by two assays, and no cytotoxic effects were observed.Infection lasted 144 h, followed by 72 h of treatment with 10 M carv, totaling 216 h of experiment.Cell viability, fibronectin (FB) expression, -SMA expression, and parasite load were evaluated. Results:Infected spheroids/organoids treated with carv showed recovery of viability compared to the infected group.Infection increased FB expression, while treatment with carv significantly reduced this effect, suggesting antifibrotic action.-SMA expression decreased in infected groups, possibly due to cytoskeletal disorganization induced by T. cruzi.In an unprecedented manner, an increase in fibrosis was observed already at early times of infection.We also observed a decrease in -SMA expression.There was a trend toward reduction of parasite load with treatment. Conclusion:The 3D cardiac spheroid/organoid model revealed, for the first time, the antifibrotic potential of carvedilol in the setting of Chagas disease, highlighting its possible therapeutic relevance.
Silva et al. (Thu,) conducted a other in Trypanosoma cruzi infection (Chagas disease). Carvedilol vs. Infected group (untreated) was evaluated on Cell viability, fibronectin expression, -SMA expression, and parasite load. Carvedilol treatment (10 M for 72 h) of T. cruzi-infected 3D cardiac spheroids recovered cell viability and significantly reduced fibronectin expression, demonstrating antifibrotic potential.