Abstract 206: A New MicroRNA Family Regulating Cardiac Autophagy and Hypertrophy
Pathologic growth of cardiomyocytes and derailed autophagy are major determinants for the development of heart failure, one of the leading medical causes of mortality worldwide. Here, we show the microRNA (miRNA)-212/132 family to regulate hypertrophy and autophagy in cardiomyocytes. Hypertrophic stimuli lead to the upregulation of miR-212 and miR-132 expression in cardiomyocytes, 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 lethality in mice. Mechanistically, 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 impaired autophagic response upon starvation. Pharmacologic miRNA inhibition by antagomir injection rescues cardiac hypertrophy and heart failure in mice, offering a possible therapeutic approach for cardiac failure.
- © 2012 by American Heart Association, Inc.