Oxidative capacity correlates with muscle mutation load in mitochondrial myopathy
Oxidative capacity correlates with muscle mutation load in mitochondrial myopathy
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DOI：
10.1002/ana.10594
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发表时间：
2003-07-01
影响因子：
11.2
通讯作者：
Vissing, J
中科院分区：
文献类型：
--
作者：
Jeppesen, TD;Schwartz, M;Vissing, J
本研究的目的是调查 24 名线粒体肌病 (MM) 患者肌肉中突变的线粒体 DNA 水平与氧化能力之间的相关性。在 17 名 mtDNA 点突变患者和 7 名 mtDNA 单一、大规模缺失（慢性进行性外眼肌麻痹 [CPEO]）患者的增量循环测试中，测量了最大摄氧量 (VO2max)、工作量 (W-max) 和静脉血浆乳酸水平。结果与 25 名健康匹配受试者的结果进行了比较。 MM 患者的突变负荷为 67 +/- 5%（范围：29 - 99%）。 VO2max 和 W-max 与异质性百分比相关 (r > 0.82；p < 0.005)，并且患者的 VO2max 和 W-max 低于健康受试者 (p < 0.000005)。运动引起的心率、通气量和静息血浆乳酸水平的峰值增加与肌肉突变负荷相关（r > 0.71；p < 0.005）。 CPEO 患者运动引起的血浆乳酸增加与肌肉突变负荷相关（r = 0.95；p < 0.005）。 CPEO 和 3243A-->G 患者的氧化能力受损，红色肌纤维参差不齐，突变负荷分别低至 45% 和 57%。研究表明，多发性骨髓瘤患者的氧化能力与骨骼肌突变负荷直接相关，并且多发性骨髓瘤患者氧化代谢受损的突变阈值水平低于体外研究中发现的水平。
The purpose of this study was to investigate the correlation between the level of mutated mitochondrial DNA in muscle and oxidative capacity in 24 patients with mitochondrial myopathy (MM). Maximal oxygen uptake (VO2max), workload (W-max), and venous plasma lactate levels were measured during an incremental cycle test to exhaustion in 17 patients with point mutations of mtDNA and in seven with single, large-scale deletions of mtDNA (chronic progressive external ophthalmoplegia [CPEO]). Results were compared with those in 25 healthy matched subjects. The mutation load in MM patients was 67 +/- 5% (range, 29 - 99%). VO2max and W-max correlated with percentage of heteroplasmy (r > 0.82; p < 0.005) and were lower in patients versus healthy subjects (p < 0.000005). Exercise-induced peak increases in heart rate, ventilation, and resting plasma lactate levels correlated with muscle mutation load (r > 0.71; p < 0.005). Exercise-induced increases in plasma lactate correlated with muscle mutation load in CPEO patients (r = 0.95; p < 0.005). Impaired oxidative capacity and ragged red muscle fibers were found in CPEO and 3243A-->G patients with mutation loads as low as 45 and 57%, respectively. The study indicates that oxidative capacity correlates directly with skeletal muscle mutation load in MM patients, and that the mutation threshold level for impaired oxidative metabolism in MM patients is lower than found in in vitro studies.