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- W2045153334 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. Atrial fibrillation and heart failure often coexist but are difficult to treat. Here the authors report a therapeutic strategy for atrial fibrillation and heart failure in mice, based on the activating effect of a small molecule, BGP-15, on IGF1 receptor signalling." @default.
- W2045153334 created "2016-06-24" @default.
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- W2045153334 date "2014-12-09" @default.
- W2045153334 modified "2023-10-14" @default.
- W2045153334 title "The small-molecule BGP-15 protects against heart failure and atrial fibrillation in mice" @default.
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- W2045153334 doi "https://doi.org/10.1038/ncomms6705" @default.
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- W2045153334 hasPublicationYear "2014" @default.
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