title: The miRNA-212/132 family regulates both cardiac hypertrophy and cardiomyocyte autophagy.
abstract: Pathological growth of cardiomyocytes (hypertrophy) is a major determinant for the development of heart failure, one of the leading medical causes of mortality worldwide. Here we show that the microRNA (miRNA)-212/132 family regulates cardiac hypertrophy and autophagy in cardiomyocytes. Hypertrophic stimuli upregulate cardiomyocyte expression of miR-212 and miR-132, which are both necessary and sufficient to drive the hypertrophic growth of cardiomyocytes. MiR-212/132 null mice are protected from pressure-overload-induced heart failure, whereas cardiomyocyte-specific overexpression of the miR-212/132 family leads to pathological cardiac hypertrophy, heart failure and death in mice. Both miR-212 and miR-132 directly target the anti-hypertrophic and pro-autophagic FoxO3 transcription factor and overexpression of these miRNAs leads to hyperactivation of pro-hypertrophic calcineurin/NFAT signalling and an impaired autophagic response upon starvation. Pharmacological inhibition of miR-132 by antagomir injection rescues cardiac hypertrophy and heart failure in mice, offering a possible therapeutic approach for cardiac failure.
authors.affiliation: Department of Molecular Cell Biology, Max Planck Institute of Biophysical Chemistry, 37077 Gottingen, Germany.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Ucar
authors.forename: Shashi K
authors.initials: SK
authors.lastname: Gupta
authors.forename: Jan
authors.initials: J
authors.lastname: Fiedler
authors.forename: Erdem
authors.initials: E
authors.lastname: Erikci
authors.forename: Michal
authors.initials: M
authors.lastname: Kardasinski
authors.forename: Sandor
authors.initials: S
authors.lastname: Batkai
authors.forename: Seema
authors.initials: S
authors.lastname: Dangwal
authors.forename: Regalla
authors.initials: R
authors.lastname: Kumarswamy
authors.forename: Claudia
authors.initials: C
authors.lastname: Bang
authors.forename: Angelika
authors.initials: A
authors.lastname: Holzmann
authors.forename: Janet
authors.initials: J
authors.lastname: Remke
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Caprio
authors.forename: Claudia
authors.initials: C
authors.lastname: Jentzsch
authors.forename: Stefan
authors.initials: S
authors.lastname: Engelhardt
authors.forename: Sabine
authors.initials: S
authors.lastname: Geisendorf
authors.forename: Carolina
authors.initials: C
authors.lastname: Glas
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Hofmann
authors.forename: Michelle
authors.initials: M
authors.lastname: Nessling
authors.forename: Karsten
authors.initials: K
authors.lastname: Richter
authors.forename: Mario
authors.initials: M
authors.lastname: Schiffer
authors.forename: Lucie
authors.initials: L
authors.lastname: Carrier
authors.forename: L Christian
authors.initials: LC
authors.lastname: Napp
authors.forename: Johann
authors.initials: J
authors.lastname: Bauersachs
authors.forename: Kamal
authors.initials: K
authors.lastname: Chowdhury
authors.forename: Thomas
authors.initials: T
authors.lastname: Thum
mesh_terms: D000818:Animals; D000070416:Antagomirs; D001343:Autophagy / Q000235:genetics*; D019703:Calcineurin / Q000235:genetics; D006332:Cardiomegaly / Q000235:genetics*; D002478:Cells, Cultured; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009841:Oligonucleotides / Q000235:genetics*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000070416:Antagomirs; C546976:MIRN132 microRNA, mouse; D035683:MicroRNAs; D009841:Oligonucleotides; C520440:antagomir-122; D019703:Calcineurin