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  The miRNA-212/132 family regulates both cardiac hypertrophy and cardiomyocyte autophagy.

Ucar, A., Gupta, S. K., Fiedler, J., Erikci, E., Kardasinski, M., Batkai, S., et al. (2012). The miRNA-212/132 family regulates both cardiac hypertrophy and cardiomyocyte autophagy. Nature Communications, 3:. doi:10.1038/ncomms2090.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-000F-F112-E Version Permalink: http://hdl.handle.net/11858/00-001M-0000-000F-F114-A
Latest Version: http://hdl.handle.net/11858/00-001M-0000-000F-F115-8
Genre: Journal Article

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 Creators:
Ucar, A.1, Author              
Gupta, S. K., Author
Fiedler, J., Author
Erikci, E.2, Author              
Kardasinski, M., Author
Batkai, S., Author
Dangwal, S., Author
Kumarswarmy, R., Author
Bang, C., Author
Holzmann, A., Author
Remke, J., Author
Caprio, M., Author
Jentzsch, C., Author
Engelhardt, S., Author
Geisendorf, S.2, Author              
Glas, C., Author
Hofmann, T. G., Author
Nessling, M., Author
Richter, K., Author
Schiffer, M., Author
Carrier, L., AuthorNapp, L. C., AuthorBauersachs, J., AuthorChowdhury, K.2, Author              Thum, T., Author more..
Affiliations:
1Research Group of Molecular Developmental Neurobiology, MPI for biophysical chemistry, Max Planck Society, escidoc:578587              
2Facility of Microarray Analyses, MPI for biophysical chemistry, Max Planck Society, escidoc:578589              

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 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.

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Language(s): eng - English
 Dates: 2012-09-25
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 Rev. Method: Peer
 Identifiers: DOI: 10.1038/ncomms2090
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Title: Nature Communications
Source Genre: Journal
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Pages: - Volume / Issue: 3 Sequence Number: 1078 Start / End Page: - Identifier: -