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Circulating miRNAs as Potential Biomarkers Associated with Cardiac Remodeling and Fibrosis in Chagas Disease
Carolina Kymie Vasques Nonaka1,2,3, Carolina Thé Macêdo2,4, Bruno Raphael Ribeiro Cavalcante1,2,3
1Center for Biotechnology and Cell Therapy, Hospital São Rafael, 41253-190 Salvador, Brazil.
Insights
Researchers identified specific microRNAs (miRNAs) that indicate disease progression in Chagas cardiomyopathy (CCC). These biomarkers could help predict which patients with Chagas disease (CD) will develop heart complications, enabling early treatment.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Parasitology
Background:
- Chagas disease (CD) affects millions globally, with 30% developing chronic Chagas cardiomyopathy (CCC).
- Current diagnostics identify infection but not individual risk for CCC progression.
- Biomarkers are needed to predict progression from indeterminate to severe cardiac forms of CD.
Purpose of the Study:
- To evaluate circulating microRNAs (miRNAs) as potential biomarkers for Chagas cardiomyopathy progression.
- To compare miRNA expression in patients with CCC, indeterminate CD, and healthy controls.
Main Methods:
- Circulating miRNAs (miR-19a-3p, miR-21-5p, miR-29b-3p, miR-30a-5p, miR-199b-5p, miR-208a-3p) were measured in 28 CCC patients, 10 indeterminate CD patients, and 10 controls.
- Correlations between miRNA levels and cardiac dysfunction markers were analyzed.
- miRNA expression was validated in cardiac tissue and studied in vitro in human cells.
Main Results:
- MiR-19a-3p, miR-21-5p, and miR-29b-3p were significantly higher in CCC patients compared to those with indeterminate CD.
- These miRNAs correlated positively with cardiac dysfunction and fibrosis, and negatively with ejection fraction.
- Increased miRNA expression was confirmed in CCC cardiac tissue and linked to cardiac hypertrophy and fibrosis in vitro.
Conclusions:
- Specific circulating miRNAs are involved in cardiac fibrosis and remodeling in Chagas disease.
- MiR-19a-3p, miR-21-5p, and miR-29b-3p show promise as predictive biomarkers for Chagas cardiomyopathy progression.
Abstract:
Chagas disease (CD) affects approximately 6-7 million people worldwide, from which 30% develop chronic Chagas cardiomyopathy (CCC), usually after being asymptomatic for years. Currently available diagnostic methods are capable of adequately identifying infected patients, but do not provide information regarding the individual risk of developing the most severe form of the disease. The identification of biomarkers that predict the progression from asymptomatic or indeterminate form to CCC, may guide early implementation of pharmacological therapy. Here, six circulating microRNAs (miR-19a-3p, miR-21-5p, miR-29b-3p, miR-30a-5p, miR-199b-5p and miR-208a-3p) were evaluated and compared among patients with CCC (n = 28), CD indeterminate form (n = 10) and healthy controls (n = 10). MiR-19a-3p, miR-21-5p, and miR-29b-3p were differentially expressed in CCC patients when compared to indeterminate form, showing a positive correlation with cardiac dysfunction, functional class, and fibrosis, and a negative correlation with ejection fraction and left ventricular strain. Cardiac tissue analysis confirmed increased expression of microRNAs in CCC patients. In vitro studies using human cells indicated the involvement of these microRNAs in the processes of cardiac hypertrophy and fibrosis. Our study suggests that miRNAs are involved in the process of cardiac fibrosis and remodeling presented in CD and indicate a group of miRNAs as potential biomarkers of disease progression in CCC.
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