The small-molecule BGP-15 protects against heart failure and atrial fibrillation in mice Academic Article uri icon

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.

authors

  • Sapra, Geeta
  • Tham, Yow Keat
  • Cemerlang, Nelly
  • Matsumoto, Aya
  • Kiriazis, Helen
  • Bernardo, Bianca C
  • Henstridge, Darren C
  • Ooi, Jenny YY
  • Pretorius, Lynette
  • Boey, Esther JH
  • Lim, Lydia
  • Sadoshima, Junichi
  • Meikle, Peter J
  • Mellet, Natalie A
  • Woodcock, Elizabeth A
  • Marasco, Silvana
  • Ueyama, Tomomi
  • Du, Xiao-Jun
  • Febbraio, Mark A
  • McMullen, Julie R

publication date

  • 2014

has subject area