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Circulating Plasma MicroRNA-208a as Potential Biomarker of Chronic Indeterminate Phase of Chagas Disease
Leandra Linhares-Lacerda1,2, Alessandra Granato1, João Francisco Gomes-Neto1
1Departamento de Imunologia, Instituto de Microbiologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Insights
Increased circulating miR-208a levels are observed in the chronic indeterminate phase of Chagas disease, suggesting its potential as a biomarker for predicting Chagas cardiomyopathy risk.
Area of Science:
- Cardiovascular Medicine
- Infectious Diseases
- Molecular Biology
Background:
- Chagas cardiomyopathy, a severe complication of chronic Chagas disease, is a major cause of death in Latin America.
- Its pathogenesis is multifactorial, involving parasite factors, immune responses, and neurogenic issues, leading to heart failure and arrhythmias.
- The chronic indeterminate phase, often asymptomatic, is now recognized as a progressive stage contributing to cardiac damage.
Purpose of the Study:
- To investigate the role of specific microRNAs in the progression of Chagas disease.
- To compare circulating levels of miR-208a and miR-34a in patients with different clinical forms of Chagas disease.
- To identify potential biomarkers for predicting the risk of developing Chagas cardiomyopathy.
Main Methods:
- Quantification of serum miR-208a and miR-34a levels in patients with Chagas disease.
- Comparison of microRNA levels between patients in the chronic indeterminate phase and those with the cardiac (CARD) clinical form.
- Analysis of microRNA expression in relation to cardiac dysfunction and disease progression.
Main Results:
- Circulating miR-208a levels were significantly elevated in the chronic indeterminate phase compared to the cardiac form.
- Serum levels of miR-34a did not show significant alterations between the groups.
- These findings suggest distinct molecular mechanisms underlying heart failure in Trypanosoma cruzi infection.
Conclusions:
- The chronic indeterminate phase of Chagas disease is an active, progressive stage contributing to cardiopathy.
- Plasma miR-208a levels show promise as a candidate biomarker for risk stratification and clinical prognosis in Chagas disease.
- Understanding microRNA dysregulation offers insights into Chagas cardiomyopathy pathogenesis.
Abstract:
Chagas cardiomyopathy is the most severe clinical manifestation of chronic Chagas disease. The disease affects most of the Latin American countries, being considered one of the leading causes of morbidity and death in the continent. The pathogenesis of Chagas cardiomyopathy is very complex, with mechanisms involving parasite-dependent cytopathy, immune-mediated myocardial damage and neurogenic disturbances. These pathological changes eventually result in cardiac myocyte hypertrophy, arrhythmias, congestive heart failure and stroke during chronic infection phase. Herein, we show that miR-208a, a microRNA that is a key factor in promoting cardiovascular dysfunction during cardiac hypertrophy processes of heart failure, has its circulating levels increased during chronic indeterminate phase when compared to cardiac (CARD) clinical forms in patients with Chagas disease. In contrast, we have not found altered serum levels of miR-34a, a microRNA known to promote pro-apoptotic role in myocardial infarction during degenerative process of cardiac injuries thus indicating intrinsic differences in the nature of the mechanisms underlying the heart failure triggered by Trypanosoma cruzi infection. Our findings support that the chronic indeterminate phase is a progressive phase involved in the genesis of chagasic cardiopathy and point out the use of plasma levels of miR-208a as candidate biomarker in risk-prediction score for the clinical prognosis of Chagas disease.
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