Document Detail


The miRNA-212/132 family regulates both cardiac hypertrophy and cardiomyocyte autophagy.
MedLine Citation:
PMID:  23011132     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Ahmet Ucar; Shashi K Gupta; Jan Fiedler; Erdem Erikci; Michal Kardasinski; Sandor Batkai; Seema Dangwal; Regalla Kumarswamy; Claudia Bang; Angelika Holzmann; Janet Remke; Massimiliano Caprio; Claudia Jentzsch; Stefan Engelhardt; Sabine Geisendorf; Carolina Glas; Thomas G Hofmann; Michelle Nessling; Karsten Richter; Mario Schiffer; Lucie Carrier; L Christian Napp; Johann Bauersachs; Kamal Chowdhury; Thomas Thum
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nature communications     Volume:  3     ISSN:  2041-1723     ISO Abbreviation:  Nat Commun     Publication Date:  2012  
Date Detail:
Created Date:  2012-09-26     Completed Date:  2013-02-01     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  101528555     Medline TA:  Nat Commun     Country:  England    
Other Details:
Languages:  eng     Pagination:  1078     Citation Subset:  IM    
Affiliation:
Department of Molecular Cell Biology, Max Planck Institute of Biophysical Chemistry, 37077 Gottingen, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Autophagy / genetics*
Calcineurin / genetics
Cardiomegaly / genetics*
Cells, Cultured
Male
Mice
Mice, Transgenic
MicroRNAs / genetics*
Myocytes, Cardiac / metabolism*
Oligonucleotides / genetics*
Rats
Reverse Transcriptase Polymerase Chain Reaction
Chemical
Reg. No./Substance:
0/MIRN132 microRNA, mouse; 0/MicroRNAs; 0/Oligonucleotides; 0/antagomir-122; EC 3.1.3.16/Calcineurin
Comments/Corrections

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