Calpain I inhibition prevents atrial structural remodeling in a canine model with atrial fibrillation
Calpain I inhibition prevents atrial structural remodeling in a canine model with atrial fibrillation作者机构：Department of Cardiology First Clinical Hospital of HarbinMedical University Harbin Heilongjiang 150001 China Department of Pharmacology and Bio-pharmaceutical KeyLaboratory of Heilongjiang Province and State Harbin MedicalUniversity Harbin Heilongjiang 150086 China Department of Uronology Second Clinical Hospital of HarbinMedical University Harbin Heilongjiang 150086 China
出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)
年 卷 期：2008年第000卷第1期
页 面：32-37页
核心收录：
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
基 金：This work was supported by grants from the National Natural Science Foundation of China (No. 30470686) the Science and Technology Specialized Research Fund for Youth of HeiJong )iang Province (No. QC06C076) key Scientific and Technological Project in Heilongjiang Province (No. GB07C32401) and the Innovation Grant of Harbin Medical University for Graduate Student (No. 200401059)
主 题：atrial fibrillation structural remodeling calpain inhibitor N-acetyl-leu-leu-met
摘 要：Background Atrial fibrillation （AF） is accompanied by atrial structural remodeling. Calpain activity is induced during AE To test a causal relationship between calpain activation and atrial structural changes, N-acetyI-Leu-Leu-Met （ALLM）, a calpain inhibitor, was utilized in a canine AF model. Methods Fifteen dogs were randomly divided into 3 groups： sham-operated group, control group and calpain inhibitor group; each with 5 dogs. Sustained AF was induced by rapid right atrium pacing at 600 beats per minute for 3 weeks. ALLM was administered at a dosage of 1.0 mg-kg-l-d1 in the calpain inhibitor group. Three weeks later, the proteolysis, protein expression of TnT and myosin, calpain I localization and expression and structural changes were examined in left atrial free walls, right atrial free walls and the interatrial septum respectively. Atrial size and contractile function were also measured by echocardiography. Results Long-term rapid atrial pacing induced marked structural changes such as enlarged atrial volume, myolysis, degradation of TnT and myosin, accumulation of glycogen and changes in mitochondrial shape and size, which were paralleled by an increase in calpain activity. The positive correlation between calpain activity and the degree of myolysis （rs=0.90 961, P〈0.0001） was demonstrated. In addition to structural abnormalities, pacing-induced atrial contractile dysfunction was observed in this study. The pacing-induced atrial structural alterations and loss of contractility were partially prevented by the calpain inhibitor ALLM. Conclusions Activation of calpain represents key features in the progression towards overt structural remodeling. Calpain inhibitor, ALLM, suppressed the increased calpain activity and reversed structural remodeling caused by sustained atrial fibrillation in the present model. Calpain inhibition may therefore provide a possibility for therapeutic intervention in AE
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