title: Overexpression of calmodulin induces cardiac hypertrophy by a calcineurin-dependent pathway.
abstract: The possible role of calcineurin in cardiac hypertrophy induced by calmodulin (CaM) overexpression in the heart was investigated. CaM transgenic (CaM-TG) mice developed marked cardiac hypertrophy and exhibited up-regulation of atrial natriuretic factor (ANF) and beta-myosin heavy chain gene expression in the heart during the first 2 weeks after birth. The activity of calcineurin in the heart was also significantly increased in CaM-TG mice compared with wild-type littermates. Treatment of CaM-TG mice with the calcineurin inhibitor FK506 (1mg/kg per day) prevented the increase in the heart-to-body weight ratio as well as that in cardiomyocyte width. FK506 also inhibited the induction of fetal-type cardiac gene expression in CaM-TG mice. Overexpression of CaM in cultured rat cardiomyocytes activated the ANF gene promoter in a manner sensitive to FK506. Activation of a calcineurin-dependent pathway thus contributes to the development of cardiac hypertrophy induced by CaM overexpression in the heart.
authors.affiliation: Department of Cardiovascular Genome Science, Nagoya University School of Medicine, Nagoya, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Obata
authors.forename: Kohzo
authors.initials: K
authors.lastname: Nagata
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Iwase
authors.forename: Mari
authors.initials: M
authors.lastname: Odashima
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Nagasaka
authors.forename: Hideo
authors.initials: H
authors.lastname: Izawa
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
authors.forename: Yoshiji
authors.initials: Y
authors.lastname: Yamada
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yokota
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism*; D006332:Cardiomegaly / Q000378:metabolism*; D002478:Cells, Cultured; D051379:Mice; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000378:metabolism*; D015398:Signal Transduction; D014018:Tissue Distribution; D015854:Up-Regulation
chemical_list: D002147:Calmodulin; D019703:Calcineurin