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

• Published in: General thoracic and cardiovascular surgery 2010-06, Vol.58 (6), p.265-270
• Main Authors: Tateishi, Atsushi, Matsushita, Masayuki, Asai, Tomohiro, Masuda, Zenichi, Kuriyama, Mitsuhito, Kanki, Kazushige, Ishino, Kozo, Kawada, Masaaki, Sano, Shunji, Matsui, Hideki
• Format: Article
• Language: English
• Subjects: Animals; Aorta, Abdominal - surgery; Atrial Natriuretic Factor - genetics; beta Catenin - metabolism; Blood Pressure; Blotting, Western; Cardiac Surgery; Cardiology; Cardiovascular Agents - pharmacology; Disease Models, Animal; Glycogen Synthase Kinase 3 - antagonists & inhibitors; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; Hypertension - complications; Hypertension - diagnostic imaging; Hypertension - drug therapy; Hypertension - enzymology; Hypertension - physiopathology; Hypertrophy, Left Ventricular - diagnostic imaging; Hypertrophy, Left Ventricular - drug therapy; Hypertrophy, Left Ventricular - enzymology; Hypertrophy, Left Ventricular - etiology; Hypertrophy, Left Ventricular - physiopathology; Kinases; Ligation; Lithium; Lithium Chloride - pharmacology; Male; Medicine; Medicine & Public Health; Original Article; Peptides; Phosphorylation; Polymerase Chain Reaction; Protein Kinase Inhibitors - pharmacology; Rats; Rats, Wistar; RNA, Messenger - metabolism; Serine; Surgical Oncology; Thoracic Surgery; Time Factors; Ultrasonography
• ISSN: 1863-6705; 1863-6713
• DOI: 10.1007/s11748-009-0505-2

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.