4180Expression profile of microRNAs in cardiac tissue from pediatric patients with heart failure (HF) supported by Ventricular Assist Device and their involvement in pathophysiological mechanisms of HF

Abstract

Abstract Background Ventricular Assist Device (VAD) has been increasingly used as bridge to transplantation for the treatment both of adult and pediatric patients with end-stage Heart Failure (HF). Several studies reported that VAD support could affect cardiac molecular mechanisms, including miRNA expression, in HF adult patients. However, little is known about the miRNA profile in pediatric HF patients supported by VAD. Purpose Aim of this study was to evaluate the effects of VAD support on expression profile of miRNAs in cardiac tissue from pediatric patients with HF, and to enrich the analysis by an in silico exploration of their potential functions and pathways. Methods Cardiac biopsies from HF children collected at the time of VAD implant [8 HF children; 57±33 (mean±SD) months; 2 males; 14.2±13.5 weight; 29±8 LVEF%] and at the time of heart transplantation after 155±33 days of VAD support [5 children; 90±46 months; 4 males; 30±15.8 weight; 38±3.9 LVEF%] were used for profiling miRNA expression by Next Generation Sequencing (NGS). Bioinformatic analyses were performed to identify the differentially expressed miRNAs in cardiac tissues after VAD support, to elucidate their potential functions (Gene Ontology), and to predict their target genes (miRWalk database). Results We identified two upregulated miRNAs (miR-29b-1-5p, miR-338-3p) and four downregulated miRNAs (miR-199a-5p, miR-199b-5p, miR-19a-3p, miR-1246) after VAD support. Gene enrichment analysis identified heart development/function, apoptosis and metabolism as main process modulated by the selected miRNAs (Fig A). Moreover, twenty genes were selected as putative miRNA targets involved in the pathophysiology of HF (Fig B). Conclusion In summary, the results of the present study suggest that modification of six miRNAs in cardiac tissue from HF children after VAD support may be involved in the regulation of several pathophysiological mechanisms underlying HF, thus providing novel perspectives for future researches.