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

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 SchifferLucie Carrier, L. Christian Napp, Johann Bauersachs, Kamal Chowdhury, Thomas Thum

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number1078
JournalNature Communications
Volume3
DOIs
Publication statusPublished - 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

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