| First Author | Sapra G | Year | 2014 |
| Journal | Nat Commun | Volume | 5 |
| Pages | 5705 | PubMed ID | 25489988 |
| Mgi Jnum | J:274567 | Mgi Id | MGI:6296527 |
| Doi | 10.1038/ncomms6705 | Citation | Sapra G, et al. (2014) The small-molecule BGP-15 protects against heart failure and atrial fibrillation in mice. Nat Commun 5:5705 |
| abstractText | Heart failure (HF) and atrial fibrillation (AF) share common risk factors, frequently coexist and are associated with high mortality. Treatment of HF with AF represents a major unmet need. Here we show that a small molecule, BGP-15, improves cardiac function and reduces arrhythmic episodes in two independent mouse models, which progressively develop HF and AF. In these models, BGP-15 treatment is associated with increased phosphorylation of the insulin-like growth factor 1 receptor (IGF1R), which is depressed in atrial tissue samples from patients with AF. Cardiac-specific IGF1R transgenic overexpression in mice with HF and AF recapitulates the protection observed with BGP-15. We further demonstrate that BGP-15 and IGF1R can provide protection independent of phosphoinositide 3-kinase-Akt and heat-shock protein 70; signalling mediators often defective in the aged and diseased heart. As BGP-15 is safe and well tolerated in humans, this study uncovers a potential therapeutic approach for HF and AF. |
