| Literature DB >> 25489988 |
Geeta Sapra1, Yow Keat Tham1, Nelly Cemerlang1, Aya Matsumoto1, Helen Kiriazis1, Bianca C Bernardo1, Darren C Henstridge1, Jenny Y Y Ooi1, Lynette Pretorius2, Esther J H Boey1, Lydia Lim1, Junichi Sadoshima3, Peter J Meikle1, Natalie A Mellet1, Elizabeth A Woodcock1, Silvana Marasco4, Tomomi Ueyama5, Xiao-Jun Du1, Mark A Febbraio2, Julie R McMullen2.
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 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.Entities:
Mesh：
Substances：
Year: 2014 PMID： 25489988 DOI： 10.1038/ncomms6705
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919