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

Yassine Sassi, Petros Avramopoulos, Deepak Ramanujam, Laurenz Grüter, Stanislas Werfel, Simon Giosele, Andreas-David Brunner, Dena Esfandyari, Aikaterini S. Papadopoulou, Bart Strooper, Norbert Hübner, Regalla Kumarswamy, Thomas Thum, Xiaoke Yin, Manuel Mayr, Bernhard Laggerbauer and Stefan Engelhardt ()
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Yassine Sassi: Technical University Munich (TUM)
Petros Avramopoulos: Technical University Munich (TUM)
Deepak Ramanujam: Technical University Munich (TUM)
Laurenz Grüter: Technical University Munich (TUM)
Stanislas Werfel: Technical University Munich (TUM)
Simon Giosele: Technical University Munich (TUM)
Andreas-David Brunner: Technical University Munich (TUM)
Dena Esfandyari: Technical University Munich (TUM)
Aikaterini S. Papadopoulou: VIB Center for the Biology of Disease, VIB
Bart Strooper: VIB Center for the Biology of Disease, VIB
Norbert Hübner: Max-Delbrüeck-Center for Molecular Medicine in the Helmholtz Association (MDC)
Regalla Kumarswamy: Hannover Medical School
Thomas Thum: Hannover Medical School
Xiaoke Yin: King’s College London
Manuel Mayr: King’s College London
Bernhard Laggerbauer: Technical University Munich (TUM)
Stefan Engelhardt: Technical University Munich (TUM)

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-01737-4

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