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Although the etiology is unknown, evidence supports immunological abnormalities, such as persistent inflammation and immune-cell activation, in a subset of patients. Since the interplay between inflammation and vascular alterations is well-established in other diseases, endothelial dysfunction has emerged as another player in ME\/CFS pathogenesis. Endothelial nitric oxide synthase (eNOS) generates nitric oxide (NO) that maintains endothelial homeostasis. eNOS is activated by silent information regulator 1 (Sirt1), an anti-inflammatory protein. Despite its relevance, no study has addressed the Sirt1\/eNOS axis in ME\/CFS. The interest in circulating microRNAs (miRs) as potential biomarkers in ME\/CFS has increased in recent years. Accordingly, we analyze a set of miRs reported to modulate the Sirt1\/eNOS axis using plasma from ME\/CFS patients. Our results show that miR-21, miR-34a, miR-92a, miR-126, and miR-200c are jointly increased in ME\/CFS patients compared to healthy controls. A similar finding was obtained when analyzing public miR data on peripheral blood mononuclear cells. Bioinformatics analysis shows that endothelial function-related signaling pathways are associated with these miRs, including oxidative stress and oxygen regulation. Interestingly, histone deacetylase 1, a protein responsible for epigenetic regulations, represented the most relevant node within the network. In conclusion, our study provides a basis to find endothelial dysfunction-related biomarkers and explore novel targets in ME\/CFS.<\/jats:p>","DOI":"10.1038\/s41598-021-89834-9","type":"journal-article","created":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T10:03:29Z","timestamp":1621418609000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Altered endothelial dysfunction-related miRs in plasma from ME\/CFS patients"],"prefix":"10.1038","volume":"11","author":[{"given":"J.","family":"Blauensteiner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Bertinat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. 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