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

Ucar A, Gupta SK, Fiedler J, Erikci E, Kardasinski M, Batkai S, Dangwal S, Kumarswamy R, Bang C, Holzmann A, Remke J, Caprio M, Jentzsch C, Engelhardt S, Geisendorf S, Glas C, Hofmann TG, Nessling M, Richter K, Schiffer M, Carrier L, Napp LC, Bauersachs J, Chowdhury K, Thum T (2012)

Publication Type: Journal article

Publication year: 2012

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 3

Article Number: 1078

DOI: 10.1038/ncomms2090

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. © 2012 Macmillan Publishers Limited. All rights reserved.

Authors with CRIS profile

Mario Schiffer

Involved external institutions

Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) Max-Planck-Institut für biophysikalische Chemie (Karl-Friedrich-Bonhoeffer-Institut) / Max Planck Institute for Biophysical Chemistry DE Germany (DE) Technische Universität München (TUM) DE Germany (DE) Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE) Ospedale San Raffaele (früher: Centro San Raffaele del Monte Tabor Foundation) IT Italy (IT)

How to cite

APA:

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

MLA:

Ucar, Ahmet, et al. "The miRNA-212/132 family regulates both cardiac hypertrophy and cardiomyocyte autophagy." Nature Communications 3 (2012).

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