Yasushige Shingu1,2, Tetsuya Hieda3, Satoshi Sugimoto4, Hidetsugu Asai5, Tomoji Yamakawa6, Satoru Wakasa3. 1. Department of Cardiovascular and Thoracic Surgery, Faculty of Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan. shingu@huhp.hokudai.ac.jp. 2. Department of Cardiovascular and Thoracic Surgery, Faculty of Medicine, Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, 060-8638, Kitaku, Sapporo, Japan. shingu@huhp.hokudai.ac.jp. 3. Department of Cardiovascular and Thoracic Surgery, Faculty of Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan. 4. Department of Cardiovascular Surgery, Obihiro Kosei Hospital, Obihiro, Japan. 5. Department of Cardiovascular Surgery, Hokkaido Medical Center for Child Health and Rehabilitation, Sapporo, Japan. 6. Department of Cardiovascular Surgery, Kinikyo Chuo Hospital, Sapporo, Japan.
Abstract
BACKGROUND: The change in myocardial protein degradation systems after ventricular unloading has been unknown. We aimed to evaluate the anti-hypertrophic protein adenosine monophosphate-activated protein kinase (AMPK) and two major protein degradation systems (ubiquitin proteasome system and autophagy) in a model of surgical ventricular reconstruction (SVR) in rats with ischemic cardiomyopathy. METHODS AND RESULTS: Rats were randomized into the following groups: sham/sham (control group), myocardial infarction (MI)/sham (sham group) and MI/SVR (SVR group), with an interval of 4 weeks. Two (early, n = 5 for each) and 28 days (late, n = 5 for each) after SVR, ventricular size, and wall stress were assessed. Myocyte area, protein expression of AMPKα and autophagy markers, and gene expression of ubiquitin ligases (Atrogin-1 and Murf-1) were evaluated in the late phase. In the early phase, left ventricular dimensions and wall stress were smaller in the SVR group than in the sham group, whereas they were comparable in the late period. Myocyte area in the SVR group was reduced to the value in the control group, while it was larger in the sham group than in the control group. Total-AMPKα, p-AMPKα, and AMPKα phosphorylation rates were higher, and Atrogin-1 and Murf-1 were lower in the SVR group than in the sham group, while the autophagy markers were not different between the groups. p-AMPKα had strong negative correlations with myocyte area, Atrogin-1, and Murf-1. CONCLUSIONS: In myocyte reverse remodeling after SVR, AMPKα phosphorylation increased in association with reduced gene expression of ubiquitin ligases.
BACKGROUND: The change in myocardial protein degradation systems after ventricular unloading has been unknown. We aimed to evaluate the anti-hypertrophic protein adenosine monophosphate-activated protein kinase (AMPK) and two major protein degradation systems (ubiquitin proteasome system and autophagy) in a model of surgical ventricular reconstruction (SVR) in rats with ischemic cardiomyopathy. METHODS AND RESULTS: Rats were randomized into the following groups: sham/sham (control group), myocardial infarction (MI)/sham (sham group) and MI/SVR (SVR group), with an interval of 4 weeks. Two (early, n = 5 for each) and 28 days (late, n = 5 for each) after SVR, ventricular size, and wall stress were assessed. Myocyte area, protein expression of AMPKα and autophagy markers, and gene expression of ubiquitin ligases (Atrogin-1 and Murf-1) were evaluated in the late phase. In the early phase, left ventricular dimensions and wall stress were smaller in the SVR group than in the sham group, whereas they were comparable in the late period. Myocyte area in the SVR group was reduced to the value in the control group, while it was larger in the sham group than in the control group. Total-AMPKα, p-AMPKα, and AMPKα phosphorylation rates were higher, and Atrogin-1 and Murf-1 were lower in the SVR group than in the sham group, while the autophagy markers were not different between the groups. p-AMPKα had strong negative correlations with myocyte area, Atrogin-1, and Murf-1. CONCLUSIONS: In myocyte reverse remodeling after SVR, AMPKα phosphorylation increased in association with reduced gene expression of ubiquitin ligases.
Authors: Makhosazane Zungu; Jonathan C Schisler; M Faadiel Essop; Chris McCudden; Cam Patterson; Monte S Willis Journal: Am J Pathol Date: 2010-12-23 Impact factor: 4.307
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