Myocardial oxidative stress, osteogenic phenotype, and energy metabolism are differentially involved in the initiation and early progression of delta-sarcoglycan-null cardiomyopathy.
Myocardial oxidative stress, osteogenic phenotype, and energy metabolism are differentially involved in the initiation and early progression of delta-sarcoglycan-null cardiomyopathy.
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DOI：
10.1007/s11010-008-9908-0
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发表时间：
2009-01
影响因子：
4.3
通讯作者：
Lee, Techung
中科院分区：
文献类型：
--
作者：
Missihoun, Comlan;Zisa, David;Shabbir, Arsalan;Lin, Huey;Lee, Techung
扩张型心肌病(DCM)是心力衰竭的常见原因，在心功能不全发生之前识别早期致病事件具有重要的机制、诊断和治疗意义。这项工作描述了缺乏δ-肌聚糖的To2品系仓鼠的早期生化发病机制。虽然TO2仓鼠的心脏在1个月龄时(症状前阶段)表现出正常的功能，但髓过氧化物酶、单核细胞趋化蛋白-1、丙二醛、骨桥蛋白和碱性磷酸酶水平明显升高，表明存在炎症、氧化应激和成骨表型。这些变化主要局限于心肌。能量代谢紊乱出现在症状期(4个月)，以催化有氧葡萄糖代谢限速步骤的丙酮酸脱氢酶E1亚基的活性和表达减弱为显著特征。因此，这项研究阐明了氧化应激、成骨表型和葡萄糖代谢在δ-肌糖蛋白缺失的扩张性心肌病的启动和早期进展中的不同参与。
Dilated cardiomyopathy (DCM) is a common cause of heart failure, and identification of early pathogenic events occurring prior to the onset of cardiac dysfunction is of mechanistic, diagnostic, and therapeutic importance. The work characterized early biochemical pathogenesis in TO2 strain hamsters lacking δ-sarcoglycan. Although the TO2 hamster heart exhibits normal function at 1 month of age (presymptomatic stage), elevated levels of myeloperoxidase, monocyte chemotactic protein-1, malondialdehyde, osteopontin, and alkaline phosphatase were evident, indicating the presence of inflammation, oxidative stress, and osteogenic phenotype. These changes were localized primarily to the myocardium. Derangement in energy metabolism was identified at the symptomatic stage (4 month), and is marked by attenuated activity and expression of pyruvate dehydrogenase E1 subunit, which catalyzes the rate-limiting step in aerobic glucose metabolism. Thus, this study illustrates differential involvement of oxidative stress, osteogenic phenotype, and glucose metabolism in the initiation and early progression of δ-sarcoglycan-null DCM.
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影响因子：
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发表时间：
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影响因子：
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