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Mitochondrial respiration in peripheral arterial disease depends on stage severity
Journal of Cellular and Molecular Medicine ( IF 5.3 ) Pub Date : 2024-03-27 , DOI: 10.1111/jcmm.18126
Fiona Speichinger 1, 2 , Alexandra Gratl 1, 3 , Ben Raude 1 , Larissa Schawe 1 , Jan Carstens 1 , Nina A. Hering 1, 2 , Andreas Greiner 1 , Dominik Pesta 4, 5, 6 , Jan Paul Frese 1
Affiliation  

Peripheral arterial disease (PAD) is an increasing cause of morbidity and its severity is graded based on clinical manifestation. To investigate the influence of the different stages on myopathy of ischemic muscle we analysed severity‐dependent effects of mitochondrial respiration in PAD. Eighteen patients with severe PAD, defined as chronic limb‐threatening ischemia, 47 patients with intermittent claudication (IC) and 22 non‐ischemic controls were analysed. High‐resolution respirometry (HRR) was performed on muscle biopsies of gastrocnemius and vastus lateralis muscle of patients in different PAD stages to investigate different respiratory states. Results from HRR are given as median and interquartile range and were normalized to citrate synthase activity (CSA), a marker for mitochondrial content. In order to account for inter‐individual differences between patients and controls, we calculated the ratio of O₂‐flux in gastrocnemius muscle over vastus muscle (‘GV ratio’). CSA of the gastrocnemius muscle as a proxy for mitochondrial content was significantly lower in critical ischemia compared to controls. Mitochondrial respiration normalized to CSA was higher in IC compared to controls. Likewise, the GV ratio was significantly higher in IC compared to control. Mitochondrial respiration and CSA of PAD patients showed stage‐dependent modifications with greater changes in the mild PAD stage group (IC).

中文翻译:

外周动脉疾病的线粒体呼吸取决于阶段的严重程度

外周动脉疾病(PAD)是发病率日益增加的原因,其严重程度根据临床表现进行分级。为了研究不同阶段对缺血性肌病的影响,我们分析了 PAD 中线粒体呼吸的严重程度依赖性影响。对 18 名严重 PAD 患者(定义为慢性肢体威胁性缺血)、47 名间歇性跛行 (IC) 患者和 22 名非缺血对照患者进行了分析。对不同PAD阶段患者的腓肠肌和股外侧肌的肌肉活检进行高分辨率呼​​吸测量(HRR),以研究不同的呼吸状态。 HRR 结果以中位数和四分位数范围给出,并标准化为柠檬酸合酶活性 (CSA)(线粒体含量的标记)。为了考虑患者和对照组之间的个体差异,我们计算了腓肠肌与股肌的 O2 通量比率(“GV 比率”)。与对照组相比,严重缺血时腓肠肌的 CSA 作为线粒体含量的代表显着降低。与对照组相比,IC 中标准化为 CSA 的线粒体呼吸更高。同样,与对照相比,IC 中的 GV 比率显着更高。 PAD 患者的线粒体呼吸和 CSA 表现出分期依赖性改变,轻度 PAD 分期组 (IC) 的变化更大。
更新日期:2024-03-27
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