EDN1 and heart failure: Indeed, NUPR1, a transcriptional regulator required for endothelin-1, is induced in human heart failure and is implicated in phenylephrine-induced hypertrophy in rat cardiomyocytes and tumor necrosis factor-induced activation of matrix metalloprotease nine in rat cardiac fibroblasts (Goruppi, Patten, Force, and Kyriakis, 2007).