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- Title
Cardiac myocyte miR-29 promotes pathological remodeling of the heart by activating Wnt signaling.
- Authors
Sassi, Yassine; Avramopoulos, Petros; Ramanujam, Deepak; Grüter, Laurenz; Werfel, Stanislas; Giosele, Simon; Brunner, Andreas-David; Esfandyari, Dena; Papadopoulou, Aikaterini S.; De Strooper, Bart; Hübner, Norbert; Kumarswamy, Regalla; Thum, Thomas; Xiaoke Yin; Mayr, Manuel; Laggerbauer, Bernhard; Engelhardt, Stefan
- 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 nonmyocyte 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 tissuespecific antimiR-29 delivery may have therapeutic value for pathological cardiac remodeling and fibrosis.
- Subjects
WNT signal transduction; CARDIAC hypertrophy; HEART fibrosis; HEART cells; HEART
- Publication
Nature Communications, 2017, Vol 8, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-017-01737-4