title: miRNA expression in pediatric failing human heart.
abstract: miRNAs are short regulatory RNAs that can regulate gene expression through interacting with the 3'UTR of target mRNAs. Although the role of miRNAs has been extensively studied in adult human and animal models of heart disease, nothing is known about their expression in pediatric heart failure patients. Different than adults with heart failure, pediatric patients respond well to phosphodiesterase inhibitor (PDEi) treatment, which is safe in the outpatient setting, results in fewer heart failure emergency department visits, fewer cardiac hospital admissions and improved NYHA classification. We have recently shown that pediatric heart failure patients display a unique molecular profile that is different from adults with heart failure. In this study we show for the first time that pediatric heart failure patients display a unique miRNA profile, and that expression of some miRNAs correlate with response to PDEi treatment. Moreover, we show that expression of Smad4, a potential target for PDEi-regulated miRNAs, is normalized in PDEi-treated patients. Since miRNAs may be used as therapy for human heart failure, our results underscore the importance of defining the molecular characteristics of pediatric heart failure patients, so age-appropriate therapy can be designed for this population.
authors: Department of Medicine/Division of Cardiology, University of Colorado School of Medicine, Aurora, CO, USA. brian.stauffer@ucdenver.edu
authors: Brian L
authors: BL
authors: Stauffer
authors: Gloria
authors: G
authors: Russell
authors: Karin
authors: K
authors: Nunley
authors: Shelley D
authors: SD
authors: Miyamoto
authors: Carmen C
authors: CC
authors: Sucharov
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism*; D006352:Heart Ventricles / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D059467:Transcriptome / Q000187:drug effects*
chemical_list: D035683:MicroRNAs; D010726:Phosphodiesterase Inhibitors