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

Fingerprint

NFATC Transcription Factors
Cardiomegaly
Pressure
Peptides
Calcineurin
Brain Natriuretic Peptide
Atrial Natriuretic Factor
Tacrolimus
Cardiac Myocytes
Cyclosporine
Rats
Chemical activation
Body Weight
Pharmacology
Weights and Measures
Serum

Keywords

  • Calcineurin
  • Cardiac hypertrophy
  • NFAT
  • Protein transduction

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

Cite this

A cell-permeable NFAT inhibitor peptide prevents pressure-overload cardiac hypertrophy. / Kuriyama, Mitsuhito; Matsushita, Masayuki; Tateishi, Atsushi; Moriwaki, Akiyoshi; Tomizawa, Kazuhito; Ishino, Kozo; Sano, Shunji; Matsui, Hideki.

In: Chemical Biology and Drug Design, Vol. 67, No. 3, 03.2006, p. 238-243.

Research output: Contribution to journalArticle

Kuriyama, Mitsuhito ; Matsushita, Masayuki ; Tateishi, Atsushi ; Moriwaki, Akiyoshi ; Tomizawa, Kazuhito ; Ishino, Kozo ; Sano, Shunji ; Matsui, Hideki. / A cell-permeable NFAT inhibitor peptide prevents pressure-overload cardiac hypertrophy. In: Chemical Biology and Drug Design. 2006 ; Vol. 67, No. 3. pp. 238-243.
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