title: Effect of inhibition of glycogen synthase kinase-3 on cardiac hypertrophy during acute pressure overload.
abstract: OBJECTIVE
  A large number of diverse signaling molecules in cell and animal models participate in the stimulus-response pathway through which the hypertrophic growth of the myocardium is controlled. However, the mechanisms of signaling pathway including the influence of lithium, which is known as an inhibitor of glycogen synthase kinase-3beta, in pressure overload hypertrophy remain unclear. The aim of our study was to determine whether glycogen synthase kinase-3beta inhibition by lithium has acute effects on the myocyte growth mechanism in a pressure overload rat model.
  
  
  METHODS
  First, we created a rat model of acute pressure overload cardiac hypertrophy by abdominal aortic banding. Protein expression time courses for beta-catenin, glycogen synthase kinase-3beta, and phosphoserine9-glycogen synthase kinase-3beta were then examined. The rats were divided into four groups: normal rats with or without lithium administration and pressure-overloaded rats with or without lithium administration. Two days after surgery, Western blot analysis of beta-catenin, echo-cardiographic evaluation, left ventricular (LV) weight, and LV atrial natriuretic peptide mRNA levels were evaluated.
  
  
  RESULTS
  We observed an increase in the level of glycogen synthase kinase-3beta phosphorylation on Ser 9. A significant enhancement of LV heart weight (P < 0.05) and interventricular septum and posterior wall thickness (P < 0.05) with pressure-overloaded hypertrophy in animals treated with lithium were also observed. Atrial natriuretic peptide mRNA levels were significantly increased with pressure overload hypertrophy in animals treated with lithium.
  
  
  CONCLUSIONS
  We have shown in an animal model that inhibition of glycogen synthase kinase-3beta by lithium has an additive effect on pressure overload cardiac hypertrophy.
authors.affiliation: Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Okayama, Japan. tate-tate@nifty.com
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tateishi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Matsushita
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Asai
authors.forename: Zenichi
authors.initials: Z
authors.lastname: Masuda
authors.forename: Mitsuhito
authors.initials: M
authors.lastname: Kuriyama
authors.forename: Kazushige
authors.initials: K
authors.lastname: Kanki
authors.forename: Kozo
authors.initials: K
authors.lastname: Ishino
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kawada
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 / Q000601:surgery; D009320:Atrial Natriuretic Factor / Q000235:genetics; D001794:Blood Pressure; D015153:Blotting, Western; D002317:Cardiovascular Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006973:Hypertension / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology; D008026:Ligation; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012694:Serine; D013997:Time Factors; D014463:Ultrasonography; D051176:beta Catenin / Q000378:metabolism
chemical_list: D002317:Cardiovascular Agents; C495268:Ctnnb1 protein, rat; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D051176:beta Catenin; D012694:Serine; D009320:Atrial Natriuretic Factor; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride