Transcriptome Analysis of Circulating microRNAs Associated With Chagas Disease Susceptibility and Chronic Chagas Cardiomyopathy Severity

BACKGROUND: Chagas disease (ChD), a major public health concern in Latin America, requires better understanding of molecular mechanisms driving disease progression and identification of biomarkers. We investigated circulating microRNAs associated with ChD susceptibility and chronic Chagas cardiomyopathy (CCC) progression. METHODS: In a cross-sectional study of 150 patients with ChD (46 indeterminate, 104 CCC) and 42 non-ChD controls, we performed microRNA sequencing, and differentiated expressed microRNAs (DEMs) were submitted to in silico functional analyses. RESULTS: We identified 40 DEMs between patients with ChD and controls, highlighting upregulated miR-143-3p and miR-223-3p, and downregulated miR-486-5p and miR-3960 in patients with ChD. These miRNAs showed involvement in immune response and cardiovascular signaling pathways. MiR-6734-5p, miR-1285-5p, miR-10527-5p, and miR-1228-5p tended to be upregulated, while miR-30c-3p tended to be downregulated in patients with severe compared to mild CCC. CONCLUSIONS: This study provides evidence for specific microRNA dysregulation in ChD, highlighting their potential as biomarkers of ChD susceptibility and CCC severity.