Myocardin induces cardiomyocyte hypertrophy

Weibing Xing, Tong Cun Zhang, Dongsun Cao, Zhigao Wang, Christopher L. Antos, Shijie Li, Yibin Wang, Eric N. Olson, Da Zhi Wang

Research output: Contribution to journalArticle

122 Scopus citations

Abstract

In response to stress signals, postnatal cardiomyocytes undergo hypertrophic growth accompanied by activation of a fetal gene program, assembly of sarcomeres, and cellular enlargement. We show that hypertrophic signals stimulate the expression and transcriptional activity of myocardin, a cardiac and smooth muscle-specific coactivator of serum response factor (SRF). Consistent with a role for myocardin as a transducer of hypertrophic signals, forced expression of myocardin in cardiomyocytes is sufficient to substitute for hypertrophic signals and induce cardiomyocyte hypertrophy and the fetal cardiac gene program. Conversely, a dominant-negative mutant form of myocardin, which retains the ability to associate with SRF but is defective in transcriptional activation, blocks cardiomyocyte hypertrophy induced by hypertrophic agonists such as phenylephrine and leukemia inhibitory factor. Myocardin-dependent hypertrophy can also be partially repressed by histone deacetylase 5, a transcriptional repressor of myocardin. These findings identify myocardin as a nuclear effector of hypertrophic signaling pathways that couples stress signals to a transcriptional program for postnatal cardiac growth and remodeling.

Original languageEnglish (US)
Pages (from-to)1089-1097
Number of pages9
JournalCirculation research
Volume98
Issue number8
DOIs
StatePublished - Apr 1 2006

Keywords

  • Cardiac hypertrophy
  • Cardiac myocytes
  • Cardiac transcription factors
  • Myocardin
  • Serum response factor
  • Transcription factors
  • Transcriptional regulation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Xing, W., Zhang, T. C., Cao, D., Wang, Z., Antos, C. L., Li, S., Wang, Y., Olson, E. N., & Wang, D. Z. (2006). Myocardin induces cardiomyocyte hypertrophy. Circulation research, 98(8), 1089-1097. https://doi.org/10.1161/01.RES.0000218781.23144.3e