A cell-permeable NFAT inhibitor peptide prevents pressure-overload cardiac hypertrophy

Mitsuhito Kuriyama, Masayuki Matsushita, Atsushi Tateishi, Akiyoshi Moriwaki, Kazuhito Tomizawa, Kozo Ishino, Shunji Sano, Hideki Matsui

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The activation of the calcineurin-nuclear factor of activated T cells cascade during the development of pressure-overload cardiac hypertrophy has been previously reported in a number of studies. In addition, numerous pharmacological studies involving calcineurin inhibitors such as FK506 and cyclosporine A have now demonstrated that these agents can prevent such hypertrophic responses in the heart. However, little is known regarding the roles of the calcineurin downstream effecter - nuclear factor of activated T cells. Our present study has further examined the roles of nuclear factor of activated T cells in pressure-overload cardiac hypertrophy by employing a recently developed cell-permeable nuclear factor of activated T cells inhibitor peptide. Rat hearts were subjected to pressure overload attributable by 4 weeks of aortic banding, and then treated with this cell-permeable nuclear factor of activated T cells inhibitor peptide and a control peptide. Treatment with the inhibitor was found to significantly decrease the heart weight/body weight ratio, the size of cardiac myocytes, and the serum brain natriuretic peptide and atrial natriuretic peptide levels. These results suggest that nuclear factor of activated T cells functions in a key role in the development of cardiac hypertrophy during pressure overload. Inhibition of nuclear factor of activated T cells by a specific inhibitor peptide is a suitable method for characterization of the molecular mechanisms underlying cardiac hypertrophy as well as in the search for new promising therapies for disease.

Original languageEnglish
Pages (from-to)238-243
Number of pages6
JournalChemical Biology and Drug Design
Volume67
Issue number3
DOIs
Publication statusPublished - Mar 2006

Keywords

  • Calcineurin
  • Cardiac hypertrophy
  • NFAT
  • Protein transduction

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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  • Cite this

    Kuriyama, M., Matsushita, M., Tateishi, A., Moriwaki, A., Tomizawa, K., Ishino, K., Sano, S., & Matsui, H. (2006). A cell-permeable NFAT inhibitor peptide prevents pressure-overload cardiac hypertrophy. Chemical Biology and Drug Design, 67(3), 238-243. https://doi.org/10.1111/j.1747-0285.2006.00360.x