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Myocardin induces cardiomyocyte hypertrophy.
Weibing Xing1, Tong-Cun Zhang, Dongsun Cao
1Carolina Cardiovascular Biology Center, Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, NC 27599-7126, USA.
Circulation Research
|March 25, 2006
Summary
Myocardin acts as a key protein in the heart, mediating cardiac hypertrophy (heart enlargement) in response to stress signals. It drives the fetal gene program essential for postnatal cardiac growth and remodeling.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Gene Regulation
Background:
- Postnatal cardiomyocytes exhibit hypertrophic growth upon stress.
- This growth involves a fetal gene program, sarcomere assembly, and cell enlargement.
- Serum response factor (SRF) is a key transcription factor in muscle cells.
Purpose of the Study:
- To investigate the role of myocardin in stress-induced cardiomyocyte hypertrophy.
- To identify myocardin as a transducer of hypertrophic signaling pathways.
- To elucidate the molecular mechanisms coupling stress signals to cardiac growth.
Main Methods:
- Studied the expression and transcriptional activity of myocardin in response to hypertrophic signals.
- Utilized forced expression of myocardin in cardiomyocytes.
- Employed a dominant-negative mutant form of myocardin.
- Investigated the effect of histone deacetylase 5 on myocardin activity.
Main Results:
- Hypertrophic signals increase myocardin expression and transcriptional activity.
- Forced myocardin expression induces cardiomyocyte hypertrophy and the fetal gene program.
- A dominant-negative myocardin mutant inhibits agonist-induced hypertrophy.
- Histone deacetylase 5 partially represses myocardin-dependent hypertrophy.
Conclusions:
- Myocardin is a nuclear effector of hypertrophic signaling pathways.
- Myocardin couples stress signals to the transcriptional program for cardiac growth.
- Myocardin plays a critical role in postnatal cardiac remodeling.