| The small-molecule BGP-15 protects against heart failure and atrial fibrillation in mice. | |
MedLine Citation:
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PMID: 25489988 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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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:
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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:
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Type: Journal Article Date: 2014-12-09 |
Journal Detail:
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Title: Nature communications Volume: 5 ISSN: 2041-1723 ISO Abbreviation: Nat Commun Publication Date: 2014 |
Date Detail:
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Created Date: 2014-12-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101528555 Medline TA: Nat Commun Country: England |
Other Details:
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Languages: eng Pagination: 5705 Citation Subset: IM |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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