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

2017; Nature Portfolio; Volume: 8; Issue: 1 Linguagem: Inglês

10.1038/s41467-017-01737-4

2041-1723

Yassine Sassi, Petros Avramopoulos, Deepak Ramanujam, Laurenz Grüter, Stanislas Werfel, Simon Giosele, Andreas‐David Brunner, Dena Esfandyari, Aikaterini S. Papadopoulou, Bart De Strooper, Norbert Hübner, Regalla Kumarswamy, Thomas Thum, Xiaoke Yin, Manuel Mayr, Bernhard Laggerbauer, Stefan Engelhardt,

Tissue Engineering and Regenerative Medicine

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.