| First Author | Balatskyi VV | Year | 2018 |
| Journal | Pflugers Arch | Volume | 470 |
| Issue | 10 | Pages | 1485-1499 |
| PubMed ID | 29923116 | Mgi Jnum | J:285938 |
| Mgi Id | MGI:6401020 | Doi | 10.1007/s00424-018-2168-2 |
| Citation | Balatskyi VV, et al. (2018) Cardiospecific deletion of alphaE-catenin leads to heart failure and lethality in mice. Pflugers Arch 470(10):1485-1499 |
| abstractText | alphaE-catenin is a component of adherens junctions that link the cadherin-catenin complex to the actin cytoskeleton. The signaling function of this protein was recently revealed. In the present study, we investigated the role of alphaE-catenin in the pathogenesis of heart failure. We mated alphaE-catenin conditional knockout mice with alphaMHC-Cre mice and evaluated their mutant offspring. We found that alphaE-catenin knockout caused enlargement of the heart and atria, fibrosis, the upregulation of hypertrophic genes, and the dysregulation of fatty acid metabolism via the transcriptional activity of Yap and beta-catenin. The activation of canonical Wnt and Yap decreased the activity of main regulators of energy metabolism (i.e., adenosine monophosphate-activated protein kinase and peroxisome proliferator-activated receptor alpha) and dysregulated hypertrophic pathway activity (i.e., phosphatidylinositide 3-kinase/Akt, cyclic adenosine monophosphate/protein kinase A, and MEK1/extracellular signal regulated kinase 1/2). The loss of alphaE-catenin also negatively affected cardio-hemodynamic function via the protein kinase A pathway. Overall, we found that the embryonic heart-specific ablation of alphaE-catenin leads to the development of heart failure with age and premature death in mice. Thus, alphaE-catenin appears to have a crucial signaling function in the postnatal heart, and the dysfunction of this gene causes heart failure through canonical Wnt and Yap activation. |
