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A Cell‐permeable NFAT Inhibitor Peptide Prevents Pressure‐Overload Cardiac Hypertrophy
Author(s) -
Kuriyama Mitsuhito,
Matsushita Masayuki,
Tateishi Atsushi,
Moriwaki Akiyoshi,
Tomizawa Kazuhito,
Ishino Kozo,
Sano Shunji,
Matsui Hideki
Publication year - 2006
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2006.00360.x
Subject(s) - nfat , pressure overload , calcineurin , muscle hypertrophy , atrial natriuretic peptide , brain natriuretic peptide , myocyte , medicine , natriuretic peptide , endocrinology , peptide , cardiac myocyte , biology , heart failure , chemistry , microbiology and biotechnology , cardiac hypertrophy , biochemistry , transplantation
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.