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The small-molecule BGP-15 protects against heart failure and atrial fibrillation in mice
Citation
Sapra, G and Tham, YK and Cemerlang, N and Matsumoto, A and Kiriazis, H and Bernardo, BC and Henstridge, DC and Ooi, JYY and Pretorius, L and Boey, EJH and Lim, L and Sadoshima, J and Meikle, PJ and Mellet, NA and Woodcock, EA and Marasco, S and Ueyama, T and Du, X-J and Febbraio, MA and McMullen, JR, The small-molecule BGP-15 protects against heart failure and atrial fibrillation in mice, Nature Communications, 5 Article 5705. ISSN 2041-1723 (2014) [Refereed Article]
Copyright Statement
Copyright 2014 Macmillan Publishers Limited
Abstract
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.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | caveolin 1, caveolin 3, collagen type 1, collagen type 3, heat shock protein 27, heat shock protein 70, o (2 hydroxy 3 piperidinopropyl) nicotinic amidoxime, phosphatidylinositol 3 kinase, protein kinase B, somatomedin C receptor, oxime |
| Research Division: | Biological Sciences |
| Research Group: | Biochemistry and cell biology |
| Research Field: | Signal transduction |
| Objective Division: | Health |
| Objective Group: | Clinical health |
| Objective Field: | Clinical health not elsewhere classified |
| UTAS Author: | Henstridge, DC (Dr Darren Henstridge) |
| ID Code: | 133351 |
| Year Published: | 2014 |
| Web of Science® Times Cited: | 67 |
| Deposited By: | Health Sciences |
| Deposited On: | 2019-06-24 |
| Last Modified: | 2019-07-23 |
| Downloads: | 0 |
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