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(Circulation. 2000;101:14.)
© 2000 American Heart Association, Inc.

Brief Rapid Communications

Augmented Cardiac Cardiotrophin-1 in Experimental Congestive Heart Failure

Michihisa Jougasaki, MD, PhD; Issei Tachibana, MD; Andreas Luchner, MD; Hanna Leskinen, MD; Margaret M. Redfield, MD; John C. Burnett, Jr, MD

From the Cardiorenal Research Laboratory, Mayo Clinic, Rochester, Minn.

Correspondence to Michihisa Jougasaki, MD, PhD, Cardiorenal Research Laboratory, Mayo Clinic, 200 First St, SW, Rochester, MN 55905. E-mail jougasaki{at}mayo.edu

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.

Key Words: genes • immunohistochemistry • hypertrophy • heart failure

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