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Ventricular cardiotrophin-1 activation precedes BNP in experimental heart failure
Michihisa Jougasaki1, Hanna Leskinen, Amy M Larsen
1Institute for Clinical Research, National Hospital Kyushu Cardiovascular Center, 8-1 Shiroyama-cho, Kagoshima 892-0853, Japan. michi@qjun.hosp.go.jp
Insights
Cardiotrophin-1 (CT-1) and B-type natriuretic peptide (BNP) gene expression increase in heart failure. Ventricular CT-1 activation precedes BNP activation during congestive heart failure progression in dogs.
Area of Science:
- Cardiovascular biology
- Molecular cardiology
- Heart failure research
Background:
- Cardiotrophin-1 (CT-1) and B-type natriuretic peptide (BNP) are cardiac biomarkers activated by cardiomyocyte stretch.
- Both CT-1 and BNP gene expression are elevated in experimental and human congestive heart failure (CHF).
Purpose of the Study:
- To investigate the cardiac gene expression patterns of CT-1 and BNP during the progression of heart failure.
- To compare the temporal activation of CT-1 and BNP genes in the failing heart.
Main Methods:
- Utilized Northern blot analysis to quantify CT-1 and BNP mRNA levels.
- Examined gene expression in normal dogs, dogs with early left ventricular dysfunction (ELVD), and dogs with overt CHF (n=5 for each group).
Main Results:
- CT-1 mRNA was detected in both atria and ventricles of normal dogs.
- Ventricular CT-1 mRNA increased progressively from ELVD to overt CHF.
- Ventricular BNP mRNA was minimally detected in normal and ELVD dogs, but markedly increased in overt CHF.
Conclusions:
- Cardiac gene expression of CT-1 and BNP is differentially regulated during CHF progression.
- Ventricular CT-1 gene activation occurs earlier than ventricular BNP gene activation in the development of CHF.
Abstract:
Both cardiotrophin-1 (CT-1) and B-type or brain natriuretic peptide (BNP) are activated by cardiomyocyte stretch, and gene expression of CT-1 and BNP are augmented in the heart in experimental and human congestive heart failure (CHF). The goal of this study was to define cardiac gene expression of CT-1 and BNP by Northern blot analysis in normal (n=5), early left ventricular dysfunction (ELVD, n=5) and overt CHF dogs (n=5), in which ventricular function is progressively decreased. CT-1 mRNA was detected in both atria and ventricles in normal dogs. Ventricular CT-1 mRNA production increased in ELVD, and it further increased in overt CHF. Ventricular BNP mRNA remained below or at the limit of detection in normal and ELVD models, and it markedly increased in overt CHF. This study reports differential regulation of gene expression of CT-1 and BNP in the heart during the progression of CHF, and demonstrates that ventricular CT-1 gene activation precedes ventricular BNP gene activation.