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.