title: Calcineurin expression, activation, and function in cardiac pressure-overload hypertrophy.
abstract: BACKGROUND
  Vascular hypertension resulting in increased cardiac load is associated with left ventricular hypertrophy and is a leading predicator for progressive heart disease. The molecular signaling pathways that respond to increases in cardiac load are poorly understood. One potential regulator of the hypertrophic response is the calcium-sensitive phosphatase calcineurin.
  
  
  RESULTS
  We showed that calcineurin enzymatic activity is increased 3. 2-fold in the heart in response to pressure-overload hypertrophy induced by abdominal aortic banding in the rat. Western blot analysis further demonstrates that calcineurin A (catalytic subunit) protein content and association with calmodulin are increased in response to pressure-overload hypertrophy. This increase in calcineurin protein content was prevented by administration of the calcineurin inhibitor cyclosporine A (CsA). CsA administration attenuated load-induced cardiac hypertrophy in a dose-dependent manner over a 14-day treatment protocol. CsA administration also partially reversed pressure-overload hypertrophy in aortic-banded rats after 14 days. CsA also attenuated the histological and molecular indexes of pressure-overload hypertrophy.
  
  
  CONCLUSIONS
  These data suggest that calcineurin is an important upstream regulator of load-induced hypertrophy.
authors.affiliation: Department of Pediatrics, Children's Hospital Medical Center, University of Cincinnati, Ohio, USA.
authors.forename: H W
authors.initials: HW
authors.lastname: Lim
authors.forename: L J
authors.initials: LJ
authors.lastname: De Windt
authors.forename: L
authors.initials: L
authors.lastname: Steinberg
authors.forename: T
authors.initials: T
authors.lastname: Taigen
authors.forename: S A
authors.initials: SA
authors.lastname: Witt
authors.forename: T R
authors.initials: TR
authors.lastname: Kimball
authors.forename: J D
authors.initials: JD
authors.lastname: Molkentin
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000378:metabolism / Q000502:physiology*; D065095:Calcineurin Inhibitors; D006332:Cardiomegaly / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D016572:Cyclosporine / Q000494:pharmacology; D018450:Disease Progression; D005260:Female; D006973:Hypertension / Q000150:complications*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D019703:Calcineurin