Augmented cardiac cardiotrophin-1 in experimental congestive heart failure

Background-Cardiotrophin-1 (CT-1) is a potent hypertrophic factor discovere d by coupling expression cloning in a mouse embryonic stem cell-based model of cardiogenesis. Methods and Results-The present study was designed to investigate the poten tial activation of atrial and ventricular CT-1 expression in pacing-induced experimental congestive heart failure (CHF) and its relationship to left v entricular hypertrophy by the method of Northern blot analysis and immunohi stochemistry. We used a canine model of pacing-induced experimental CHF bas ed 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 im munostaining in the atrial and ventricular cardiomyocytes from both normal and CHF hearts. CT-1 immunoreactivity was more intense in the atrium and ve ntricle from CHF hearts than in normal hearts. Conclusions-The present study demonstrates that both atrium and ventricle s ynthesize CT-1 and that cardiac production of CT-1 is augmented in a canine model of experimental CHF, This study also demonstrates that ventricular C T-1 mRNA correlates with left ventricular hypertrophy, suggesting that CT-1 plays an important role in the structural remodeling that characterizes CH F.