| First Author | Le Dour C | Year | 2017 |
| Journal | Hum Mol Genet | Volume | 26 |
| Issue | 2 | Pages | 333-343 |
| PubMed ID | 28069793 | Mgi Jnum | J:241598 |
| Mgi Id | MGI:5903167 | Doi | 10.1093/hmg/ddw389 |
| Citation | Le Dour C, et al. (2017) Decreased WNT/beta-catenin signalling contributes to the pathogenesis of dilated cardiomyopathy caused by mutations in the lamin a/C gene. Hum Mol Genet 26(2):333-343 |
| abstractText | Cardiomyopathy caused by lamin A/C gene (LMNA) mutations (hereafter referred as LMNA cardiomyopathy) is characterized by cardiac conduction abnormalities and left ventricular systolic dysfunction predisposing to heart failure. Previous cardiac transcriptional profiling of LmnaH222P/H222P mouse, a small animal model of LMNA cardiomyopathy, suggested decreased WNT/beta-catenin signalling. We confirmed decreased WNT/beta-catenin signalling in the hearts of these mice by demonstrating decreased beta-catenin and WNT proteins. This was correlated with increased expression of soluble Frizzled-related proteins that modulate the WNT/beta-catenin signalling pathway. Hearts of LmnaH222P/H222P mice also demonstrated lowered expression of the gap junction connexin 43. Activation of WNT/beta-catenin activity with 6-bromoindirubin-3'-oxime improved cardiac contractility and ameliorated intraventricular conduction defects in LmnaH222P/H222P mice, which was associated with increased expression of myocardial connexin 43. These results indicate that decreased WNT/beta-catenin contributes to the pathophysiology of LMNA cardiomyopathy and that drugs activating beta-catenin may be beneficial in affected individuals. |
