Effects of Urocortin 2 Versus Urocortin 3 Gene Transfer on Left Ventricular Function and Glucose Disposal

Dimosthenis Giamouridis, Mei Hua Gao, N. Chin Lai, Zhen Tan, Young Chul Kim, Tracy Guo, Atsushi Miyanohara, W. Matthijs Blankesteijn, Erik Biessen, H. Kirk Hammond
JACC: Basic to Translational Science2018
UCn2 and UCn3 peptides have recently been infused to treat patients with heart failure (HF) but are limited by their short half-lives. A 1-time intravenous injection of virus vectors encoding UCn2 or UCn3 provided sustained increases in plasma concentrations of the peptides. This was associated with increases in both systolic and diastolic left ventricular (LV) function, mediated by increased LV SERCA2a expression and Ca2+handling. UCn2, but not UCn3, gene transfer reduced fasting glucose and increased glucose disposal. These findings support UCn2 and UCn3 gene transfer as potential treatments for HF and indicate that UCn2 may be an optimal selection in patients with diabetes and HF.
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