Cardiac myocyte miR-29 promotes pathological remodeling of the heart by activating Wnt signaling.
Yassine SassiPetros AvramopoulosDeepak RamanujamLaurenz GrüterStanislas WerfelSimon GioseleAndreas-David BrunnerDena EsfandyariAikaterini S PapadopoulouBart De StrooperNorbert HübnerRegalla KumarswamyThomas ThumXiaoke YinManuel MayrBernhard LaggerbauerStefan EngelhardtPublished in: Nature communications (2017)
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.
Keyphrases
- cell proliferation
- long non coding rna
- left ventricular
- long noncoding rna
- mouse model
- poor prognosis
- stem cells
- gene expression
- squamous cell carcinoma
- low dose
- signaling pathway
- dna methylation
- atrial fibrillation
- neoadjuvant chemotherapy
- lymph node
- copy number
- electronic health record
- genome wide
- bone marrow
- locally advanced
- heat stress