Effect of inhibition of glycogen synthase kinase-3 on cardiac hypertrophy during acute pressure overload

Atsushi Tateishi, Masayuki Matsushita, Tomohiro Asai, Zenichi Masuda, Mitsuhito Kuriyama, Kazushige Kanki, Kozo Ishino, Masaaki Kawada, Shunji Sano, Hideki Matsui

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13 Citations (Scopus)

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-3β, in pressure overload hypertrophy remain unclear. The aim of our study was to determine whether glycogen synthase kinase-3β 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 β-catenin, glycogen synthase kinase-3β, and phosphoserine9-glycogen synthase kinase-3β 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 β-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-3β 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-3β by lithium has an additive effect on pressure overload cardiac hypertrophy.

Original languageEnglish
Pages (from-to)265-270
Number of pages6
JournalGeneral Thoracic and Cardiovascular Surgery
Volume58
Issue number6
DOIs
Publication statusPublished - Jun 2010

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Keywords

  • Cardiac hypertrophy
  • Glycogen synthase kinase-3β
  • Lithium
  • Wnt
  • β-Catenin

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Tateishi, A., Matsushita, M., Asai, T., Masuda, Z., Kuriyama, M., Kanki, K., Ishino, K., Kawada, M., Sano, S., & Matsui, H. (2010). Effect of inhibition of glycogen synthase kinase-3 on cardiac hypertrophy during acute pressure overload. General Thoracic and Cardiovascular Surgery, 58(6), 265-270. https://doi.org/10.1007/s11748-009-0505-2