A XXXX signature in the failing heart.

@entity1 @entity712 @entity6 @entity2240 @entity5 @entity19 @entity17341 @entity299 @entity4149 @entity413 @entity2388
A salient feature of the failing heart is metabolic remodeling towards predominant @entity413 metabolism and activation of the fetal gene program. @entity2240 is a multitargeted receptor @entity4149 kinase inhibitor used for the treatment of highly vascularized @entity5 . In @entity6 @entity1 , @entity2240 significantly decreases blood @entity413 . However, a considerable proportion of @entity2240 -treated @entity1 develop @entity299 or failure. We asked whether @entity2240 treatment results in shift towards glycolysis in the heart. @entity413 uptake by the heart was increased fivefold in @entity19 treated with @entity2240 . Transcript analysis by qPCR revealed an induction of genes associated with glycolysis and reactivation of the fetal gene program. Additionally, we observed a shift in the enzyme @entity2388 kinase from the adult M1 (PKM1) isoform to the fetal M2 ( @entity17341 ) isoform, a hallmark of the Warburg Effect. This novel observation led us to examine whether a similar shift occurs in @entity1 @entity712 . Examination of tissue from @entity1 with @entity712 similarly displayed an induction of @entity17341 . Moreover, this phenomenon was partially reversed following mechanical unloading. We propose that @entity2388 kinase isoform switching represents a novel feature of the fetal gene program in the failing heart.
