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Published on: January 27, 2019
Alterations in Cardiac Metabolism by Trypanosoma cruzi Infection: A Metabolomic Assessment by RPLC-MS and GC-MS
Hanna Carvalho de Sá1, Breno Cardim Barreto2,3, Maria Vitória Gomes das Neves3
1Department of Analytical Chemistry, Institute of Chemistry, Federal University of Bahia, Salvador, BA 40170-115, Brazil.
Insights
Chagas disease (CD) causes cardiac death. Metabolomics revealed altered energy metabolism, amino acids, and inflammation in infected mouse hearts, suggesting new therapeutic targets for this parasitic infection.
Area of Science:
- Cardiovascular Research
- Parasitology
- Metabolomics
Background:
- Chagas disease (CD), caused by *Trypanosoma cruzi*, is a major cause of cardiac mortality in Latin America.
- The precise mechanisms driving CD pathogenesis and cardiac complications remain incompletely understood.
- Understanding metabolic shifts during infection is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the metabolic alterations in the heart during the acute phase of Chagas disease.
- To identify key metabolic pathways affected by *Trypanosoma cruzi* infection.
- To correlate metabolic changes with cardiac pathology.
Main Methods:
- Untargeted metabolomics analysis of cardiac tissues from infected and healthy mice.
- Comparison of metabolite profiles at 60 days postinfection.
- Pathway enrichment analysis to identify dysregulated metabolic routes.
Main Results:
- 251 significant metabolites or chemical classes were identified.
- Observed disturbances in energy metabolism and amino acid regulation.
- Increased inflammatory markers (eicosanoids) and sphingomyelin accumulation correlated with myocarditis.
Conclusions:
- Metabolic reprogramming plays a significant role in Chagas disease cardiac pathology.
- Identified metabolic signatures provide insights into disease progression and heart damage.
- Findings may guide the development of novel therapeutic strategies for Chagas disease.
Abstract:
Chagas disease (CD), caused by Trypanosoma cruzi, has been one of the leading causes of cardiac death in Latin America. Its pathogenesis and progression are still poorly understood. Thus, we performed an untargeted metabolomics analysis to understand the metabolic changes involved in the final acute phase of CD. Male mice's chagasic hearts (60 days postinfection) were compared to healthy tissues. Two hundred and fifty-one significant metabolites or chemical classes were annotated. Disturbances in energy metabolism and dysregulation of amino acids were observed. Pathway analyses indicated increased inflammatory activity in infected individuals, as observed by eicosanoid (prostaglandin and thromboxane) changes. The accumulation of some sphingomyelins, correlated with myocarditis, suggests heart tissue damage from the infection. The metabolic changes observed contribute to understanding disease progression and the cardiac effects caused by the parasite, bringing new insights into the discovery and development of new therapies.
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