Neuromuscular Junction Damage in the Calf Muscles of Patients With Advanced Peripheral Artery Disease.

IF 4 2区医学 Q1 CLINICAL NEUROLOGY

Neuropathology and Applied Neurobiology Pub Date : 2025-02-01 DOI:10.1111/nan.70008

Huiyin Tu, Ali H Hakim, Julian K Kim, Zhen Zhu, Yuqian Tian, Iraklis I Pipinos, Yu-Long Li

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Abstract

Aims: Peripheral artery disease (PAD) reduces blood flow to the legs and causes severe muscle and leg dysfunction for PAD patients. Skeletal muscle contractile function is dependent on the health of the muscle itself and that of the neuromuscular junction (NMJ) on the muscle membrane.

Methods: To determine whether the NMJ, including the motor nerve terminals and nicotinic acetylcholine receptors (nAChR), is damaged in PAD, gastrocnemius muscles were collected from 3 controls and 13 PAD patients to capture images from 331 control NMJs and 512 PAD NMJs.

Results: For the motor nerve terminals, there were more denervated nAChR clusters and fewer nerve terminal occupancies in NMJs in PAD patients, compared with controls. For the nAChR clusters in the NMJs, the area per nAChR cluster was 369.3 ± 6.7 versus 225.2 ± 5.3 μm², the area per fragment was 195.9 ± 9.2 versus 107.1 ± 3.1 μm², the number of fragments per nAChR cluster was 2.3 ± 0.1 versus 3.2 ± 0.1, the nAChR cluster area per endplate area was 75.7 ± 1.6 versus 55.7 ± 1.1%, total distance of fragments per nAChR cluster was 4.6 ± 0.4 versus 8.8 ± 0.8 μm, and the fragmented nAChR clusters were 7.6% versus 21.6% of total nAChR clusters in controls versus PAD patients, respectively (p < 0.05 in all parameters).

Conclusions: Our data demonstrate deterioration of the motor nerve terminals and nAChR clusters, which may compromise neuromuscular transmission, and contribute to the severe leg dysfunction observed in patients with PAD.

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晚期外周动脉疾病患者小腿肌肉的神经肌肉连接损伤

目的：外周动脉疾病（PAD）减少流向腿部的血液，导致PAD患者严重的肌肉和腿部功能障碍。骨骼肌的收缩功能取决于肌肉本身和肌膜上的神经肌肉连接（NMJ）的健康状况。方法：为确定PAD患者包括运动神经末梢和烟碱受体（nAChR）在内的NMJ是否受损，收集3例对照组和13例PAD患者腓骨肌，采集331例对照组NMJ和512例PAD NMJ图像。结果：与对照组相比，PAD患者运动神经末梢失神经nAChR簇增多，神经末梢占位减少。NMJs中nAChR簇的面积分别为369.3±6.7 μm2和225.2±5.3 μm2，每个片段面积分别为195.9±9.2 μm2和107.1±3.1 μm2，每个nAChR簇的片段数分别为2.3±0.1和3.2±0.1，nAChR簇面积每个终板面积分别为75.7±1.6和55.7±1.1%，每个nAChR簇的片段总距离分别为4.6±0.4和8.8±0.8 μm。结论：我们的数据表明运动神经末梢和nAChR簇的恶化可能损害神经肌肉传递，并导致PAD患者观察到严重的腿部功能障碍。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuropathology and Applied Neurobiology 医学-病理学

CiteScore

8.20

自引率

2.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Neuropathology and Applied Neurobiology is an international journal for the publication of original papers, both clinical and experimental, on problems and pathological processes in neuropathology and muscle disease. Established in 1974, this reputable and well respected journal is an international journal sponsored by the British Neuropathological Society, one of the world leading societies for Neuropathology, pioneering research and scientific endeavour with a global membership base. Additionally members of the British Neuropathological Society get 50% off the cost of print colour on acceptance of their article.