CONICET | Buscador de Institutos y Recursos Humanos

The biomarker value of circulating microRNAs (miRNAs) present in the bloodstream has been extensively studied since the discovery of these small non-coding RNA molecules that regulate gene expression. MicroRNA dysregulation has been linked to cancer development, cardiovascular and neurological diseases, lipid metabolism, and impaired immunity. Our study was designed to evaluate miRNA expression levels in individuals chronically infected with Trypanosoma cruzi showing different degrees of cardiac damage by Next Generation Sequencing Technologies (small-RNA-seq). Chronic chagasic patients with different degrees of cardiac involvement were classified as: Indeterminate (IND, n=5); Moderate (M, n=5) and Severe (S, n=5). Parallel sex and age-matched healthy volunteers (Co, n=5). miRNAs were extracted from human plasma using standard protocols and sequenced by Illumina MiSeq system. Finally, sequencing results were processed and analyzed by open software and databases such as Bowtie, R, samtools, ensembl.org and mirbase.org. These analyses revealed high abundance of miRNA expression in chromosome 7 in S vs Co (fold change), in agreement with previous results indicating a positive correlation between this chromosome and heart diseases. miRNASeq also showed differential expression of mature miRNAs in IND, M and S compared to Co. On the other hand, most of the smallRNA found among samples correspond to y-RNA, which has been involved in chromosomal DNA replication and cellular responses to stress, making of them new potential diagnostic biomarkers. miRNAs differentially expressed associated to heart failure (S) correspond to miRNA let-7f-5p, miRNA 125a-5p and miRNA 142-3p. Our results show an association between the presence of specific miRNA and the severity of chronic chagasic cardiomyopathy. New studies are needed for their use of follow-up and prognosis markers of the evolution of this disease.