ArticlePLoS neglected tropical diseases2012
Oral administration of GW788388, an inhibitor of transforming growth factor beta signaling, prevents heart fibrosis in Chagas disease.
Article in PLoS neglected tropical diseases, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 37 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Neuroprotective Treatments for Digestive Forms of Chagas Disease in Experimental Models: A Systematic Review.Oxidative medicine and cellular longevity · 2022Pooled it
- Regulatory roles of PIWI-interacting RNAs in cardiovascular disease.American journal of physiology. Heart and circulatory physiology · 2025Review
- Research progress of connexin 43 in cardiovascular diseases.Frontiers in cardiovascular medicine · 2025Review
- Pirfenidone Prevents Heart Fibrosis during Chronic Chagas Disease Cardiomyopathy.International journal of molecular sciences · 2024Article
- Retraction: Oral Administration of GW788388, an Inhibitor of Transforming Growth Factor Beta Signaling, Prevents Heart Fibrosis in Chagas Disease.PLoS neglected tropical diseases · 2024Article
- Cardiac arrhythmogenesis: roles of ion channels and their functional modification.Frontiers in physiology · 2024Review
- Vaccine-linked chemotherapy improves cardiac structure and function in a mouse model of chronic Chagas disease.Frontiers in cellular and infection microbiology · 2023Article
- Oxidized High-Density Lipoprotein Induces Endothelial Fibrosis Promoting Hyperpermeability, Hypotension, and Increased Mortality.Antioxidants (Basel, Switzerland) · 2022Article
- Genetic Disruption of Guanylyl Cyclase/Natriuretic Peptide Receptor-A Triggers Differential Cardiac Fibrosis and Disorders in Male and Female Mutant Mice: Role of TGF-β1/SMAD Signaling Pathway.International journal of molecular sciences · 2022Article
- Suppression of TGF-β/Smad2 signaling by GW788388 enhances DENV-2 clearance in macrophages.Journal of medical virology · 2022Article
- Emerging Antiarrhythmic Drugs for Atrial Fibrillation.International journal of molecular sciences · 2022Review
- Review
- The Atrium in Atrial Fibrillation - A Clinical Review on How to Manage Atrial Fibrotic Substrates.Frontiers in cardiovascular medicine · 2022Review
- In Chagas disease, transforming growth factor beta neutralization reducesFrontiers in cellular and infection microbiology · 2022Article
- Transforming growth factor-ß as a therapeutic target for the cardiac damage of Chagas disease.Memorias do Instituto Oswaldo Cruz · 2022Article
- Alterations to the Cardiac Metabolome Induced by ChronicACS infectious diseases · 2021Article
- The Search for Biomarkers and Treatments in Chagas Disease: Insights From TGF-Beta Studies and Immunogenetics.Frontiers in cellular and infection microbiology · 2021Review
- TGF-β Pathway in Salivary Gland Fibrosis.International journal of molecular sciences · 2020Review
- Therapeutic Targets for the Treatment of Cardiac Fibrosis and Cancer: Focusing on TGF-β Signaling.Frontiers in cardiovascular medicine · 2020Review
- Article
Corrections and comments
- Retraction · 2024-07-23Duplication of/in Image · Error in Image · Investigation by Journal/Publisher · Objections by Author(s) · Unreliable Data · Unreliable Results and/or Conclusions ·
- Retracted
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChagas disease induced by Trypanosoma cruzi (T. cruzi) infection is a major cause of mortality and morbidity affecting the cardiovascular system for which presently available therapies are largely inadequate. Transforming Growth Factor beta (TGFß) has been involved in several regulatory steps of T. cruzi invasion and in host tissue fibrosis. GW788388 is a new TGFß type I and type II receptor kinase inhibitor that can be orally administered. In the present work, we studied its effects in vivo during the acute phase of experimental Chagas disease. METHODOLOGY/PRINCIPAL
findingsMale Swiss mice were infected intraperitoneally with 10(4) trypomastigotes of T. cruzi (Y strain) and evaluated clinically. We found that this compound given once 3 days post infection (dpi) significantly decreased parasitemia, increased survival, improved cardiac electrical conduction as measured by PR interval in electrocardiography, and restored connexin43 expression. We could further show that cardiac fibrosis development, evaluated by collagen type I and fibronectin expression, could be inhibited by this compound. Interestingly, we further demonstrated that administration of GW788388 at the end of the acute phase (20 dpi) still significantly increased survival and decreased cardiac fibrosis (evaluated by Masson's trichrome staining and collagen type I expression), in a stage when parasite growth is no more central to this event. CONCLUSION/SIGNIFICANCE: This work confirms that inhibition of TGFß signaling pathway can be considered as a potential alternative strategy for the treatment of the symptomatic cardiomyopathy found in the acute and chronic phases of Chagas disease.
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Registered trials
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