Urocortin-3 Gene Transfer Increases Function of the Failing Heart in Mice

Urocortin 3 (UCn3), a member of the corticotropin releasing factor family, has beneficial effects on cardiac function. Long term therapy using this peptide is encumbered by its short half-life, ~5 minutes, which can be resolved by gene transfer. We have shown that heart function was increased by a single intravenous (IV) injection of an adeno-associated virus 8 encoding UCn2 (AAV8.UCn2) or UCn3 (AAV8.UCn3) in normal mice. Furthermore, UCn2 gene transfer (GT) ameliorated function of the failing mouse heart. In the current study, we explore the effects of UCn3 gene transfer in heart failure. Our hypothesis was that UCn3 gene transfer would increase function of the failing heart in mice. Heart failure was induced by cryoinjury in 10w-old C57Bl/6 male mice. Three weeks later heart function was assessed by echocardiography and mice with ejection fraction (EF) <40% were randomly assigned to receive IV saline (control), or IV AAV8.UCn3 (5×1011 gc/mouse). Five weeks after randomization, mice that received UCn3 GT...