title: Differential regulation of microRNAs in end-stage failing hearts is associated with left ventricular assist device unloading.
abstract: Mechanical unloading by left ventricular assist devices (LVADs) in advanced heart failure (HF), in addition to improving symptoms and end-organ perfusion, is supposed to stimulate cellular and molecular responses which can reverse maladaptive cardiac remodeling. As microRNAs (miRNAs) are key regulators in remodeling processes, a comparative miRNA profiling in transplanted hearts of HF patients with/without LVAD assistance could aid to comprehend underlying molecular mechanisms. Next generation sequencing (NGS) was used to analyze miRNA differential expression in left ventricles of HF patients who underwent heart transplantation directly (n = 9) or following a period of LVAD support (n = 8). After data validation by quantitative real-time PCR, association with functional clinical parameters was investigated. Bioinformatics' tools were then used for prediction of putative targets of modulated miRNAs and relative pathway enrichment. The analysis revealed 13 upregulated and 10 downregulated miRNAs in failing hearts subjected to LVAD assistance. In particular, the expression level of some of them (miR-338-3p, miR-142-5p and -3p, miR-216a-5p, miR-223-3p, miR-27a-5p, and miR-378g) showed correlation with off-pump cardiac index values. Predicted targets of these miRNAs were involved in focal adhesion/integrin pathway and in actin cytoskeleton regulation. The identified miRNAs might contribute to molecular regulation of reverse remodeling and heart recovery mechanisms.
authors.affiliation: Institute of Clinical Physiology, National Research Council, CNR, Via Moruzzi 1, 56124 Pisa, Italy ; Institute of Life Sciences, Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56127 Pisa, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Barsanti
authors.affiliation: Institute of Clinical Physiology, National Research Council, CNR, Via Moruzzi 1, 56124 Pisa, Italy.
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Trivella
authors.affiliation: Laboratory of Integrative Systems Medicine, National Research Council, Via Moruzzi 1, 56124 Pisa, Italy.
authors.forename: Romina
authors.initials: R
authors.lastname: D'Aurizio
authors.affiliation: Laboratory of Integrative Systems Medicine, National Research Council, Via Moruzzi 1, 56124 Pisa, Italy.
authors.forename: Mariama
authors.initials: M
authors.lastname: El Baroudi
authors.affiliation: Fritz Lipmann Institute for Age Research, Leibniz Institute, Beutenbergstraße 11, 07745 Jena, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Baumgart
authors.affiliation: Fritz Lipmann Institute for Age Research, Leibniz Institute, Beutenbergstraße 11, 07745 Jena, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Groth
authors.affiliation: Institute of Clinical Physiology, National Research Council, Cardiothoracic and Vascular Department, Niguarda Ca' Granda Hospital, Piazza Ospedale Maggiore 3, 20162 Milan, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Caruso
authors.affiliation: Institute of Clinical Physiology, National Research Council, Cardiothoracic and Vascular Department, Niguarda Ca' Granda Hospital, Piazza Ospedale Maggiore 3, 20162 Milan, Italy ; Cardiothoracic and Vascular Department, Niguarda Ca' Granda Hospital, Piazza Ospedale Maggiore 3, 20162 Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Verde
authors.affiliation: Cardiothoracic and Vascular Department, Niguarda Ca' Granda Hospital, Piazza Ospedale Maggiore 3, 20162 Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Botta
authors.affiliation: Institute of Clinical Physiology, National Research Council, Cardiothoracic and Vascular Department, Niguarda Ca' Granda Hospital, Piazza Ospedale Maggiore 3, 20162 Milan, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Cozzi
authors.affiliation: Institute of Clinical Physiology, National Research Council, CNR, Via Moruzzi 1, 56124 Pisa, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Pitto
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006333:Heart Failure / Q000150:complications / Q000235:genetics* / Q000517:prevention & control*; D006353:Heart-Assist Devices; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000235:genetics* / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D035683:MicroRNAs