title: MicroRNAs in the human heart: a clue to fetal gene reprogramming in heart failure.
abstract: BACKGROUND
  Chronic heart failure is characterized by left ventricular remodeling and reactivation of a fetal gene program; the underlying mechanisms are only partly understood. Here we provide evidence that cardiac microRNAs, recently discovered key regulators of gene expression, contribute to the transcriptional changes observed in heart failure.
  
  
  RESULTS
  Cardiac transcriptome analyses revealed striking similarities between fetal and failing human heart tissue. Using microRNA arrays, we discovered profound alterations of microRNA expression in failing hearts. These changes closely mimicked the microRNA expression pattern observed in fetal cardiac tissue. Bioinformatic analysis demonstrated a striking concordance between regulated messenger RNA expression in heart failure and the presence of microRNA binding sites in the respective 3' untranslated regions. Messenger RNAs upregulated in the failing heart contained preferentially binding sites for downregulated microRNAs and vice versa. Mechanistically, transfection of cardiomyocytes with a set of fetal microRNAs induced cellular hypertrophy as well as changes in gene expression comparable to the failing heart.
  
  
  CONCLUSIONS
  Our data support a novel mode of regulation for the transcriptional changes in cardiac failure. Reactivation of a fetal microRNA program substantially contributes to alterations of gene expression in the failing human heart.
authors.affiliation: University of Würzburg, University Hospital, Department of Internal Medicine I, Cardiology, Würzburg, Germany. Thum_T@klinik.uni-wuerzburg.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Thum
authors.forename: Paolo
authors.initials: P
authors.lastname: Galuppo
authors.forename: Christian
authors.initials: C
authors.lastname: Wolf
authors.forename: Jan
authors.initials: J
authors.lastname: Fiedler
authors.forename: Susanne
authors.initials: S
authors.lastname: Kneitz
authors.forename: Linda W
authors.initials: LW
authors.lastname: van Laake
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Doevendans
authors.forename: Christine L
authors.initials: CL
authors.lastname: Mummery
authors.forename: Jürgen
authors.initials: J
authors.lastname: Borlak
authors.forename: Axel
authors.initials: A
authors.lastname: Haverich
authors.forename: Carina
authors.initials: C
authors.lastname: Gross
authors.forename: Stefan
authors.initials: S
authors.lastname: Engelhardt
authors.forename: Georg
authors.initials: G
authors.lastname: Ertl
authors.forename: Johann
authors.initials: J
authors.lastname: Bauersachs
mesh_terms: D000328:Adult; D001665:Binding Sites / Q000235:genetics; D005318:Fetal Heart / Q000378:metabolism / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006333:Heart Failure / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics*
chemical_list: D035683:MicroRNAs