title: A cell-permeable NFAT inhibitor peptide prevents pressure-overload cardiac hypertrophy.
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 effector--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.
authors.affiliation: Department of Physiology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
authors.forename: Mitsuhito
authors.initials: M
authors.lastname: Kuriyama
authors.forename: Masayuki
authors.initials: M
authors.lastname: Matsushita
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tateishi
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Moriwaki
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Tomizawa
authors.forename: Kozo
authors.initials: K
authors.lastname: Ishino
authors.forename: Shunji
authors.initials: S
authors.lastname: Sano
authors.forename: Hideki
authors.initials: H
authors.lastname: Matsui
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000503:physiopathology; D009320:Atrial Natriuretic Factor / Q000097:blood; D019703:Calcineurin / Q000096:biosynthesis / Q000235:genetics; D006332:Cardiomegaly / Q000503:physiopathology* / Q000517:prevention & control*; D002463:Cell Membrane Permeability / Q000187:drug effects; D008297:Male; D050778:NFATC Transcription Factors / Q000037:antagonists & inhibitors* / Q000502:physiology; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009842:Oligopeptides / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D050778:NFATC Transcription Factors; D009842:Oligopeptides; C121611:VIVIT peptide; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D019703:Calcineurin