Document Detail


The small-molecule BGP-15 protects against heart failure and atrial fibrillation in mice.
MedLine Citation:
PMID:  25489988     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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.
Authors:
Geeta Sapra; Yow Keat Tham; Nelly Cemerlang; Aya Matsumoto; Helen Kiriazis; Bianca C Bernardo; Darren C Henstridge; Jenny Y Y Ooi; Lynette Pretorius; Esther J H 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
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Publication Detail:
Type:  Journal Article     Date:  2014-12-09
Journal Detail:
Title:  Nature communications     Volume:  5     ISSN:  2041-1723     ISO Abbreviation:  Nat Commun     Publication Date:  2014  
Date Detail:
Created Date:  2014-12-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101528555     Medline TA:  Nat Commun     Country:  England    
Other Details:
Languages:  eng     Pagination:  5705     Citation Subset:  IM    
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