PLASMA EXPRESSION LEVEL OF miRNA IS POSITIVELY ASSOCIATED WITH CHAGAS CARDIOMYOPATHY IN PATIENTS WITH CHAGAS DISEASE

VILLAR SILVINA R; FRANCISCO CALLEJAS; ANA ROSA PEREZ; JUAN BELOSCAR; OSCAR BOTTASSO; MANUEL FRESNO; NURIA GIRONES

Buenos Aires

Congreso; Reunion Conjunta de Sociedades de Biociencia; 2017

PLASMAEXPRESSION LEVEL OF miRNA IS POSITIVELY ASSOCIATED WITH CHAGASCARDIOMYOPATHY IN PATIENTS WITH CHAGAS DISEASESilvina R Villar1; Francisco Callejas Hernandez2;Ana R Pérez1, Juan Beloscar3; Oscar Bottasso1,Manuel Fresno2 and Núria Gironès2. 1Instituto de Inmunología Clínica y Experimental deRosario (IDICER UNR-CONICET), Rosario, Argentina. 2 Centro de BiologíaMolecular Severo Ochoa, (CSIC UAM), Madrid, España. 3Cátedra y Servicio de Cardiología, Sección Chagas,Hospital Provincial del Centenario, Universidad Nacional de Rosario, ArgentinaE-mail: villar_silvina@hotmail.com; villar@idicer-conicet.gob.ar  The biomarker value of circulating microRNAs (miRNAs) present in thebloodstream has been extensively studied since the discovery of these smallnon-coding RNA molecules that regulate gene expression. MicroRNA dysregulation has been linked tocancer development, cardiovascular and neurological diseases, lipid metabolism,and impaired immunity. Our study was designed to evaluate miRNA expressionlevels in individuals chronically infected with Trypanosoma cruzishowing different degrees of cardiac damage by Next Generation SequencingTechnologies (small-RNA-seq). Chronic chagasic patients with different degreesof 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 andsequenced by Illumina MiSeq system. Finally, sequencing results were processedand analyzed by open software and databases such as Bowtie, R, samtools,ensembl.org and mirbase.org. These analyses revealed high abundance of miRNAexpression in chromosome 7 in S vs Co (fold change), in agreement with previousresults indicating a positive correlation between this chromosome and heartdiseases. 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 amongsamples correspond to y-RNA, which has been involved in chromosomal DNAreplication and cellular responses to stress, making of them new potentialdiagnostic biomarkers. miRNAs differentially expressed associated to heartfailure (S) correspond to miRNA let-7f-5p, miRNA 125a-5p and miRNA 142-3p. Ourresults show an association between the presence of specific miRNA and theseverity of chronic chagasic cardiomyopathy. New studies are needed for theiruse of follow-up and prognosis markers of the evolution of this disease. Keywords: Chagas disease; miRNAs; Next Generation Sequencing Technologies