Augmented cardiac cardiotrophin-1 in experimental congestive heart failure

Background - Cardiotrophin-1 (CT-1) is a potent hypertrophic factor discovered by coupling expression cloning in mouse embryonic stem cell-based model of cardiogenesis. Methods and Results - The present study was designed to investigate the potential activation of atrial and ventricular CT- 1 expression in pacing-induced experimental congestive heart failure (CHF) and its relationship to left ventricular hypertrophy by the method of Northern blot analysis and immunohistochemistry. We used a canine model of pacing- induced experimental CHF based on hemodynamic and neurohumoral characteristics that closely mimic human dilated cardiomyopathy. Northern blot analysis demonstrated that CT-1 gene expression was present in normal atrium and ventricle and was increased in CHF hearts. There was a positive correlation between ventricular CT-1 mRNA and left ventricular mass index. Immunohistochemistry revealed positive immunostaining in the atrial and ventricular cardiomyocytes from both normal and CHF hearts. CT-1 immunoreactivity was more intense in the atrium and ventricle from CHF hearts than in normal hearts. Conclusions - The present study demonstrates that both atrium and ventricle synthesize CT-1 and that cardiac production of CT-1 is augmented in a canine model of experimental CHF. This study also demonstrates that ventricular CT-mRNA correlates with left ventricular hypertrophy, suggesting that CT-1 plays an important role in the structural remodeling that characterizes CHF.