Cardiotrophin 1 (CT-1)

Cardiotrophin-1 (CT-1) is a 201 amino acid member of the interleukin-6 superfamily. It was identified by its ability to induce hypertrophic response in cardiac myocytes. CT-1 mRNA levels were found both in cardiac myocytes and in cardiac nonmyocytes. CT-1 was also detected in abundance in normal adult human lung and was expressed in both fetal and adult airway smooth muscle cells. CT-1activates gp130 dependent signaling and stimulates the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway to transduce hypertrophic and cytoprotective signals in cardiac myocytes. CT-1 has also a neurotrophic function. CT-1 deficiency causes increased motoneuron cell death in spinal cord and brainstem nuclei of mice during a period between embryonic day 14 and the first postnatal week.

Moreover, CT-1 is a hepatocyte survival factor that efficiently reduces hepatocellular damage in animal models of acute liver injury. CT-1 expression is augmented after hypoxic stimulation and it can protect cardiac cells when added either prior to simulated ischaemia or at the time of reoxygenation following simulated ischaemia. CT-1 can induce expression of the protective heat shock proteins (hsps) in cardiac cells. Cardiotrophin-1 increased ventricular expression of ANP, brain natriuretic peptide (BNP) and angiotensinogen mRNA. CT-1 levels were significantly elevated in patients with heart failure, patients with dilatative cardiomyopathy, moderate/severe mitral regurgitation, stable and unstable angina and after acute myocardial infarction.