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Journal Article

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

MPS-Authors
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Ucar,  A.
Research Group of Molecular Developmental Neurobiology, MPI for biophysical chemistry, Max Planck Society;

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Erikci,  E.
Facility of Microarray Analyses, MPI for biophysical chemistry, Max Planck Society;

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Geisendorf,  S.
Facility of Microarray Analyses, MPI for biophysical chemistry, Max Planck Society;

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Chowdhury,  K.
Facility of Microarray Analyses, MPI for biophysical chemistry, Max Planck Society;

External Ressource
Fulltext (public)

1546215.pdf
(Publisher version), 2MB

Supplementary Material (public)

1546215_s1.pdf
(Supplementary material), 5MB

Citation

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: 1078. doi:10.1038/ncomms2090.


Cite as: http://hdl.handle.net/11858/00-001M-0000-000F-F112-E
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.