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Nat Commun. 2017 Nov 20;8(1):1614. doi: 10.1038/s41467-017-01737-4.

Cardiac myocyte miR-29 promotes pathological remodeling of the heart by activating Wnt signaling.

Author information

1
Institute of Pharmacology and Toxicology, Technical University Munich (TUM), 80802, Munich, Germany.
2
Mount Sinai, Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
3
DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, 80802, Munich, Germany.
4
VIB Center for the Biology of Disease, VIB, 3000, Leuven, Belgium.
5
Center for Human Genetics and Leuven Institute for Neurodegenerative Disorders (LIND), KU Leuven and Universitaire Ziekenhuizen, 3000, Leuven, Belgium.
6
Cardiovascular and Metabolic Sciences, Max-Delbrüeck-Center for Molecular Medicine in the Helmholtz Association (MDC), 13125, Berlin, Germany.
7
DZHK (German Center for Cardiovascular Research), Partner Site Berlin, 10115, Berlin, Germany.
8
Charité-Universitätsmedizin, 10117, Berlin, Germany.
9
Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, 30625, Hannover, Germany.
10
King's British Heart Foundation Centre, King's College London, SE5 9NU, London, UK.
11
Institute of Pharmacology and Toxicology, Technical University Munich (TUM), 80802, Munich, Germany. stefan.engelhardt@tum.de.
12
DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, 80802, Munich, Germany. stefan.engelhardt@tum.de.

Abstract

Chronic cardiac stress induces pathologic hypertrophy and fibrosis of the myocardium. The microRNA-29 (miR-29) family has been found to prevent excess collagen expression in various organs, particularly through its function in fibroblasts. Here, we show that miR-29 promotes pathologic hypertrophy of cardiac myocytes and overall cardiac dysfunction. In a mouse model of cardiac pressure overload, global genetic deletion of miR-29 or antimiR-29 infusion prevents cardiac hypertrophy and fibrosis and improves cardiac function. Targeted deletion of miR-29 in cardiac myocytes in vivo also prevents cardiac hypertrophy and fibrosis, indicating that the function of miR-29 in cardiac myocytes dominates over that in non-myocyte cell types. Mechanistically, we found cardiac myocyte miR-29 to de-repress Wnt signaling by directly targeting four pathway factors. Our data suggests that, cell- or tissue-specific antimiR-29 delivery may have therapeutic value for pathological cardiac remodeling and fibrosis.

PMID:
29158499
PMCID:
PMC5696364
DOI:
10.1038/s41467-017-01737-4
[Indexed for MEDLINE]
Free PMC Article

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