Cardiotrophin-1 in heart failure.

Cardiotrophin-1 (CT-1) is a 201 amino acid 1 member of the interleukin (IL)-6 cytokine superfamily, which includes leukemia inhibitory factor (LIF), ciliary neurotrophic factor, IL-11, and oncostatin M.2 Cardiotrophin-1 was discovered by Pennica et al2 via expression cloning of mouse embryoid bodies, using a cardiac myocyte hypertrophy screen to identify positive clones. CT-1 has hypertrophic and cardioprotective properties and acts through LIF receptor /glycoprotein 130 (gp130)-coupled signaling pathways. The LIF receptor binds CT-1, and then gp130 associates with the ligand-receptor complex and transduces the proximal signal. CT-1 intracellular signaling pathways include extracellular signal regulated kinases (ERK), mitogen activated protein (MAP) kinases, the janus kinase (JAK)/signal transducers and activators of transcription (STAT) system, and PI3-kinase/Akt. Downstream mediators of CT-1’s cellular effects include multiple ERK-coupled transcription factors, STAT-3, nuclear factorB, and heat shock proteins 56, 70, and 90. Cardiac CT-1 expression is increased by hypoxia, where it protects cardiac myocytes from ischemic and reperfusion injury and apoptosis.