ArticlePLoS neglected tropical diseases2019
TGF-β inhibitor therapy decreases fibrosis and stimulates cardiac improvement in a pre-clinical study of chronic Chagas' heart disease.
Article in PLoS neglected tropical diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- SBC Guideline on the Diagnosis and Treatment of Patients with Cardiomyopathy of Chagas Disease - 2023.Arquivos brasileiros de cardiologia · 2023Guideline
- Therapeutic Targets for Myocardial Fibrosis: A Comprehensive Review of Current and Emerging Approaches.Cardiovascular & hematological disorders drug targets · 2026Review
- The Role of Immunogenetics in the Host-Parasite Interaction of Chagas Disease: Implications for Personalized Medicine.Tropical medicine and infectious disease · 2025Review
- Regulatory roles of PIWI-interacting RNAs in cardiovascular disease.American journal of physiology. Heart and circulatory physiology · 2025Review
- System-based insights into parasitological and clinical treatment failure in Chagas disease.mSystems · 2025Review
- Exercise training reduces cardiac fibrosis, promoting improvement in arrhythmias and cardiac dysfunction in an experimental model of chronic chagasic cardiomyopathy.Frontiers in physiology · 2025Article
- Monocyte-derived extracellular vesicles, stimulated by Trypanosoma cruzi, enhance cellular invasion in vitro via activated TGF-β1.Journal of extracellular vesicles · 2024Article
- Review
- Pirfenidone Prevents Heart Fibrosis during Chronic Chagas Disease Cardiomyopathy.International journal of molecular sciences · 2024Article
- Hitting the Target! Challenges and Opportunities for TGF-β Inhibition for the Treatment of Cardiac fibrosis.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Article
- Genetic Ablation and Pharmacological Blockade of Bradykinin B1 Receptor Unveiled a Detrimental Role for the Kinin System in Chagas Disease Cardiomyopathy.Journal of clinical medicine · 2023Article
- Treatment with benznidazole and pentoxifylline regulates microRNA transcriptomic profile in a murine model of Chagas chronic cardiomyopathy.PLoS neglected tropical diseases · 2023Article
- The AP-1 transcription factor Fosl-2 drives cardiac fibrosis and arrhythmias under immunofibrotic conditions.Communications biology · 2023Article
- State-of-the-Art in the Drug Discovery Pathway for Chagas Disease: A Framework for Drug Development and Target Validation.Research and reports in tropical medicine · 2023Review
- Article
- Upregulated miR-18a-5p in Colony Forming Unit-Hill's in Subclinical Cardiovascular Disease and Metformin Therapy; MERIT Study.Biomedicines · 2022Article
- Insights from the use of erythropoietin in experimental Chagas disease.International journal for parasitology. Drugs and drug resistance · 2022Article
- Transforming growth factor-β in myocardial disease.Nature reviews. Cardiology · 2022Review
- Emerging Antiarrhythmic Drugs for Atrial Fibrillation.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TGF-β involvement in Chagas disease cardiomyopathy has been clearly demonstrated. The TGF-β signaling pathway is activated in the cardiac tissue of chronic phase patients and is associated with an increase in extracellular matrix protein expression. The aim of this study was to investigate the effect of GW788388, a selective inhibitor of TβR1/ALK5, on cardiac function in an experimental model of chronic Chagas' heart disease. To this end, C57BL/6 mice were infected with Trypanosoma cruzi (102 parasites from the Colombian strain) and treated orally with 3mg/kg GW788388 starting at 120 days post-infection (dpi), when 100% of the infected mice show cardiac damage, and following three distinct treatment schedules: i) single dose; ii) one dose per week; or iii) three doses per week during 30 days. The treatment with GW788388 improved several cardiac parameters: reduced the prolonged PR and QTc intervals, increased heart rate, and reversed sinus arrhythmia, and atrial and atrioventricular conduction disorders. At 180 dpi, 30 days after treatment interruption, the GW3x-treated group remained in a better cardiac functional condition. Further, GW788388 treatment reversed the loss of connexin-43 enriched intercellular plaques and reduced fibrosis of the cardiac tissue. Inhibition of the TGF-β signaling pathway reduced TGF-β/pSmad2/3, increased MMP-9 and Sca-1, reduced TIMP-1/TIMP-2/TIMP-4, and partially restored GATA-6 and Tbox-5 transcription, supporting cardiac recovery. Moreover, GW788388 administration did not modify cardiac parasite load during the infection but reduced the migration of CD3+ cells to the heart tissue. Altogether, our data suggested that the single dose schedule was not as effective as the others and treatment three times per week during 30 days seems to be the most effective strategy. The therapeutic effects of GW788388 are promising and suggest a new possibility to treat cardiac fibrosis in the chronic phase of Chagas' heart disease by TGF-β inhibitors.
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