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 a 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-1 mRNA correlates with left ventricular hypertrophy, suggesting that CT-1 plays an important role in the structural remodeling that characterizes CHF.[1]References
- Augmented cardiac cardiotrophin-1 in experimental congestive heart failure. Jougasaki, M., Tachibana, I., Luchner, A., Leskinen, H., Redfield, M.M., Burnett, J.C. Circulation (2000) [Pubmed]
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