In healthy individuals, physical exercise improves cardiovascular health and muscle strength, alleviates fatigue and reduces the risk of chronic diseases. Although exercise is suggested as a lifestyle intervention to manage various chronic illnesses, it negatively affects people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), who suffer from exercise intolerance. We hypothesized that altered extracellular vesicle (EV) signalling in ME/CFS patients after an exercise challenge may contribute to their prolonged and exacerbated negative response to exertion (post-exertional malaise). EVs were isolated by size exclusion chromatography from the plasma of 18 female ME/CFS patients and 17 age- and BMI-matched female sedentary controls at three time points: before, 15 min, and 24 h after a maximal cardiopulmonary exercise test. EVs were characterized using nanoparticle tracking analysis and their protein cargo was quantified using Tandem Mass Tag-based (TMT) proteomics. The results show that exercise affects the EV proteome in ME/CFS patients differently than in healthy individuals and that changes in EV proteins after exercise are strongly correlated with symptom severity in ME/CFS. Differentially abundant proteins in ME/CFS patients versus controls were involved in many pathways and systems, including coagulation processes, muscle contraction (both smooth and skeletal muscle), cytoskeletal proteins, the immune system and brain signalling.

中文翻译：

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女性肌痛性脑脊髓炎/慢性疲劳综合征病例中细胞外囊泡蛋白货物的失调以及对最大运动的反应的久坐控制

对于健康的人来说，体育锻炼可以改善心血管健康和肌肉力量，减轻疲劳并降低患慢性病的风险。尽管运动被建议作为一种生活方式干预措施来控制各种慢性疾病，但它会对患有肌痛性脑脊髓炎/慢性疲劳综合症（ME/CFS）的人产生负面影响，这些人患有运动不耐受。我们假设，ME/CFS 患者在运动挑战后细胞外囊泡 (EV) 信号的改变可能导致他们对运动的负面反应延长并加剧（运动后不适）。通过尺寸排阻色谱法，在三个时间点从 18 名女性 ME/CFS 患者和 17 名年龄和 BMI 匹配的女性久坐对照者的血浆中分离出 EV：最大心肺运动测试前、15 分钟和后 24 小时。使用纳米颗粒跟踪分析对 EV 进行表征，并使用基于串联质量标签 (TMT) 的蛋白质组学对它们的蛋白质货物进行定量。结果表明，运动对 ME/CFS 患者 EV 蛋白质组的影响与健康个体不同，并且运动后 EV 蛋白质的变化与 ME/CFS 症状严重程度密切相关。ME/CFS 患者与对照组的差异丰度蛋白质涉及许多途径和系统，包括凝血过程、肌肉收缩（平滑肌和骨骼肌）、细胞骨架蛋白、免疫系统和大脑信号传导。