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

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...

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Bibliographic Details
Published in:Nature communications Vol. 3; no. 1; p. 1078
Main Authors: Ucar, Ahmet, Gupta, Shashi K., Fiedler, Jan, Erikci, Erdem, Kardasinski, Michal, Batkai, Sandor, Dangwal, Seema, Kumarswamy, Regalla, Bang, Claudia, Holzmann, Angelika, Remke, Janet, Caprio, Massimiliano, Jentzsch, Claudia, Engelhardt, Stefan, Geisendorf, Sabine, Glas, Carolina, Hofmann, Thomas G., Nessling, Michelle, Richter, Karsten, Schiffer, Mario, Carrier, Lucie, Napp, L. Christian, Bauersachs, Johann, Chowdhury, Kamal, Thum, Thomas
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 25.09.2012
Nature Publishing Group
Nature Pub. Group
Subjects:
631/337/384/331
631/443/592/1540
631/80/39
692/308
Animals
Autophagy - genetics
Calcineurin - genetics
Cardiomegaly - genetics
Cells, Cultured
Humanities and Social Sciences
Male
Mice
Mice, Transgenic
MicroRNAs - genetics
multidisciplinary
Myocytes, Cardiac - metabolism
Oligonucleotides - genetics
Rats
Reverse Transcriptase Polymerase Chain Reaction
Science
Science (multidisciplinary)
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary: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. Heart failure is often a consequence of pathological growth of cardiomyocytes or cardiac hypertrophy. Here Ucar and colleagues report that the microRNAs miR-132 and miR-212 promote cardiac hypertrophy and inhibit autophagy in cardiomyocytes by downregulating the transcription factor FoxO3.
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ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms2090