Dysregulation of extracellular vesicle protein cargo in female myalgic encephalomyelitis/chronic fatigue syndrome cases

[L'engle]

https://pubmed.ncbi.nlm.nih.gov/38173127/​

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Dysregulation of extracellular vesicle protein cargo in female myalgic encephalomyelitis/chronic fatigue syndrome cases and sedentary controls in response to maximal exercise​

Ludovic Giloteaux 1 , Katherine A Glass 1 , Arnaud Germain 1 , Carl J Franconi 1 , Sheng Zhang 2 , Maureen R Hanson 1

Affiliations

• PMID: 38173127
• PMCID: PMC10764978
• DOI: 10.1002/jev2.12403

Abstract​

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.

Keywords: ME/CFS; chronic fatigue syndrome; exercise; extracellular vesicle cargo; myalgic encephalomyelitis; proteomics.

© 2024 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.

https://pubmed.ncbi.nlm.nih.gov/38173127/

 

[L'engle]

Condensed version on Health Rising:

https://www.healthrising.org/blog/2...igue-syndrome-extracellular-vesicle-exercise/

Ranging in size from 30-1,000 nanometers, extracellular vesicles are vanishingly small (a human hair is 80,000- 100,000 nanometers wide) packages that are regularly being emitted by our cells. They’re so tiny that it took the development of electron microscopes and ultracentrifuges to find them, but once they were found, they turned out to be everywhere and they pack a punch.

Their hypothesis was that studying EVs released during/after exercise would help inform what’s happens during exercise and what may be causing the post-exertional malaise people that ME/CFS experience

Giloteaux et al. found the ME/CFS patients’ EVs were “highly disrupted” – and in a familiar way – compared to the sedentary but healthy controls (HC’s). The study found:

1. Fewer proteins in EVs 15 after exercise in patients compared to controls (Figure 4a).
2. Reduced protein expression in EVs after exercise in ME/CFS patients (63 increased EV proteins in ME/CFS vs 178 E in HCs).
3. Delayed response – a delayed increase in the abundance of several EV proteins after exercise.

The authors concluded that the ME/CFS patients exhibited a “failure to mount an adequate response to exercise at the molecular level.” The theme was a familiar one. In her exercise studies, Hanson’s group has found the same pattern with regard to proteins, metabolites, and gene expression in ME/CFS patients: for some reason, their systems are simply unable at the molecular level to respond to exercise.