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Updated: Jul 6, 2026
08:25
Transverse Aortic Constriction in Mice
Published on: April 21, 2010
Raf-1 kinase is required for cardiac hypertrophy and cardiomyocyte survival in response to pressure overload
Ian S Harris1, Shaosong Zhang, Ilya Treskov
1Center for Cardiovascular Research, Department of Internal Medicine, Washington University School of Medicine, St Louis, Mo, USA.
Circulation
|August 4, 2004
Summary
Raf-1 kinase activity is crucial for preventing cardiac hypertrophy and cardiomyocyte death during heart pressure overload. Inhibiting Raf-1 in mice led to increased mortality and resistance to hypertrophy.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Signaling Pathways
Background:
- Cardiac hypertrophy, a response to pressure overload, increases mortality.
- Mechanical stress activates signaling pathways like Ras/Raf-1/MEK/ERK in the heart.
Purpose of the Study:
- To investigate the role of Raf-1 serine/threonine kinase in cardiac hypertrophy pathogenesis.
- To determine if Raf-1 is essential for the heart's response to pressure overload.
Main Methods:
- Generated transgenic mice with cardiac-specific dominant-negative Raf-1 (DN-Raf).
- Assessed cardiac structure, function, and signaling pathways (ERK, JNK, p38 MAPK) under pressure overload (aortic banding).
Main Results:
- DN-Raf mice showed inhibited ERK activation but normal JNK/p38 MAPK activation under pressure overload.
- DN-Raf mice experienced increased cardiomyocyte apoptosis and mortality (>35%) within 7 days.
- Surviving DN-Raf mice were resistant to cardiac hypertrophy and hypertrophic gene induction.
Conclusions:
- Raf-1 kinase activity is essential for cardiac hypertrophy development in response to pressure overload.
- Raf-1 kinase activity is vital for cardiomyocyte survival under pressure overload conditions.
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