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The small-molecule BGP-15 protects against heart failure and atrial fibrillation in mice

Citation

Sapra, G and Tham, YK and Cemerlang, N and Matsumoto, A and Kiriazis, H and Bernardo, BC and Henstridge, DC and Ooi, JYY and Pretorius, L and Boey, EJH and Lim, L and Sadoshima, J and Meikle, PJ and Mellet, NA and Woodcock, EA and Marasco, S and Ueyama, T and Du, X-J and Febbraio, MA and McMullen, JR, The small-molecule BGP-15 protects against heart failure and atrial fibrillation in mice, Nature Communications, 5 Article 5705. ISSN 2041-1723 (2014) [Refereed Article]

Copyright Statement

Copyright 2014 Macmillan Publishers Limited

DOI: 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 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.

Item Details

Item Type:Refereed Article
Keywords:caveolin 1, caveolin 3, collagen type 1, collagen type 3, heat shock protein 27, heat shock protein 70, o (2 hydroxy 3 piperidinopropyl) nicotinic amidoxime, phosphatidylinositol 3 kinase, protein kinase B, somatomedin C receptor, oxime
Research Division:Biological Sciences
Research Group:Biochemistry and Cell Biology
Research Field:Signal Transduction
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cardiovascular System and Diseases
UTAS Author:Henstridge, DC (Mr Darren Henstridge)
ID Code:133351
Year Published:2014
Web of Science® Times Cited:35
Deposited By:Health Sciences
Deposited On:2019-06-24
Last Modified:2019-07-23
Downloads:0

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