10.4225/03/581ad3d37d52a Geeta Sapra Geeta Sapra Yow Keat Tham Yow Keat Tham Nelly Cemerlang Nelly Cemerlang Aya Matsumoto Aya Matsumoto Helen Kiriazis Helen Kiriazis Bianca Bernardo Bianca Bernardo Darren Henstridge Darren Henstridge Jenny Ooi Jenny Ooi Lynette Pretorius Lynette Pretorius Esther Boey Esther Boey Lydia Lim Lydia Lim Junichi Sadoshima Junichi Sadoshima Peter Meikle Peter Meikle Natalie Mellet Natalie Mellet Elizabeth Woodcock Elizabeth Woodcock Silvana Marasco Silvana Marasco Tomomi Ueyama Tomomi Ueyama Xiao-Jun Du Xiao-Jun Du Mark Febbraio Mark Febbraio Julie McMullen Julie McMullen The small-molecule BGP-15 protects against heart failure and atrial fibrillation in mice Monash University 2016 Atrial Fibrillation Heart Failure Cardiology Cardiology (incl. Cardiovascular Diseases) 2016-11-03 06:06:07 Journal contribution https://bridges.monash.edu/articles/journal_contribution/The_small-molecule_BGP-15_protects_against_heart_failure_and_atrial_fibrillation_in_mice/4198215 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.