Journal article
The small-molecule BGP-15 protects against heart failure and atrial fibrillation in mice
Geeta Sapra, Yow Keat Tham, Nelly Cemerlang, Aya Matsumoto, Helen Kiriazis, Bianca C Bernardo, Darren C Henstridge, Jenny YY Ooi, Lynette Pretorius, Esther JH Boey, Lydia Lim, Junichi Sadoshima, Peter J Meikle, Natalie A Mellet, Elizabeth A Woodcock, Silvana Marasco, Tomomi Ueyama, Xiao-Jun Du, Mark A Febbraio, Julie R McMullen
Nature Communications | NATURE RESEARCH | Published : 2014
DOI: 10.1038/ncomms6705
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 dem..
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Awarded by National Health and Medical Research Council (NHMRC)
Awarded by NHMRC Research Fellows
Awarded by Australia Research Council Future Fellowship
Awarded by National Heart Foundation Fellowship
Funding Acknowledgements
We thank Professor Garry Jennings for helpful discussions and Thawin Pongsukwechkul (Baker IDI) for technical assistance. This study was funded by National Health and Medical Research Council (NHMRC) Project Grants (1008682 to JRM and 1004441 to MAF), Diabetes Australia Research Trust (J.R.M.), Paceline Inc., and supported in part by the Victorian Government's Operational Infrastructure Support Program. X.-J.D., P.J.M., E.A.W., M.A.F. and J.R.M. are NHMRC Research Fellows (IDs 1043026-SRF, 1042095-SRF, 586621-PRF, 1021168-SPRF, 586604-SRF). J.R.M. and D.C.H. were also supported by an Australia Research Council Future Fellowship (FT0001657) and National Heart Foundation Fellowship (PF 10M5347), respectively.