Altered endothelial dysfunction-related miRs in plasma from ME/CFS patients.

Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease characterized by unexplained debilitating fatigue. 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.