期刊
NATURE COMMUNICATIONS
卷 5, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/ncomms6705
关键词
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资金
- National Health and Medical Research Council (NHMRC) [1008682, 1004441]
- Diabetes Australia Research Trust
- Paceline Inc.
- Victorian Government's Operational Infrastructure Support Program
- NHMRC Research Fellows [1043026-SRF, 1042095-SRF, 586621-PRF, 1021168-SPRF, 586604-SRF]
- Australia Research Council Future Fellowship [FT0001657]
- National Heart Foundation Fellowship [PF 10M5347]
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.
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