Transcriptome analysis of circulating microRNAs associated with Chagas disease susceptibility and chronic Chagas cardiomyopathy severity
Chagas disease (CD), 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. We investigated the association of circulating microRNAs (miRNAs) with CD susceptibility and heart disease progression. A multicentric prospective observational study was conducted with 150 CD patients (46 indeterminate, 104 CCC [chronic chagasic cardiomyopathy] staged A-D) and 42 healthy controls from CD endemic areas. Sequencing of circulating miRNAs was performed, and differential expression analyses were conducted. We identified 40 differentially expressed miRNAs between CD patients and healthy 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 CD 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. This study provides evidence for the dysregulation of specific miRNAs in CD, highlighting their potential role in disease pathophysiology and possible use as biomarkers for CD susceptibility and CCC severity. Overall design: miRNA-seq profiling total RNA extracted from human serum of samples from patients of Chagas Disease in indeterminate and chronic Chagas cardiomyopathy