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.


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.
Jougasaki
M
M
Cardiorenal Research Laboratory, Mayo Clinic, Rochester, MN 55905, USA. jougasaki@mayo.edu
Tachibana
I
I
Luchner
A
A
Leskinen
H
H
Redfield
M M
MM
Burnett
J C
JC
D000818:Animals; D015152:Blotting, Northern; D002311:Cardiomyopathy, Dilated / Q000378:metabolism / Q000503:physiopathology; D016207:Cytokines / Q000032:analysis / Q000235:genetics*; D004195:Disease Models, Animal; D004285:Dogs; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology*; D006352:Heart Ventricles; D006439:Hemodynamics; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics
D016207:Cytokines; D012333:RNA, Messenger; C092073:cardiotrophin 1