Transcriptome analysis of circulating microRNAs associated with Chagas disease susceptibility and chronic Chagas cardiomyopathy severity

BackgroundChagas disease (ChD), caused by infection with the protozoan parasite Trypanosoma cruzi, is a major public health concern in Latin America. Understanding the molecular mechanisms driving disease progression and identifying biomarkers are crucial. ObjectiveWe investigated the association of circulating microRNAs (miRNAs) with ChD susceptibility and chronic Chagas cardiomyopathy (CCC) progression. MethodsA multicentric prospective observational study was conducted with 150 ChD patients (46 indeterminate form, 104 CCC staged A-D) and 42 non-ChD controls from ChD endemic areas from Rio de Janeiro, and Posse in Brazil. Sequencing of circulating miRNAs was performed, and differential expression analyses were conducted. The differentiated miRNAs were submitted to functional analyses related to immune response and cardiovascular signaling pathways. ResultsWe identified 40 differentially expressed miRNAs between ChD patients and non-ChD controls, highlighting miR-199b-5p, miR-153-3p, miR-143-3p, and miR-223-3p upregulated, and miR-150-3p, miR-4508, miR-486-5p, and miR-3960, downregulated in ChD patients. Moreover, functional analysis using Ingenuity Pathway Analysis software revealed that these miRNAs were involved in immune response and cardiovascular signaling pathways. Several miRNAs (miR-6734-5p, miR-1285-5p, miR-10527-5p, miR-31-5p, miR-5187-5p, miR-6515-5p) tended to present a higher expression in patients with severe compared to those with mild CCC, while miR-30c-2-3p presented lower expression in these groups. ConclusionThis study provides evidence for the dysregulation of specific miRNAs in ChD, highlighting their potential role in disease pathophysiology and possible use as biomarkers of ChD susceptibility and CCC severity.