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

Authors

J Blauensteiner, R Bertinat, L E León, M Riederer, N Sepúlveda, F Westermeier

Institution

Institute of Biomedical Science, FH Joanneum University of Applied Sciences, Graz, Austria

Publication

Scientific Reports, 2021 May 19; 11:10604

Key findings

  • The levels of five microRNAs (molecules which help cells create proteins) were increased in people with ME/CFS compared with healthy controls.
  • These specific microRNAs are all involved in controlling the endothelium (the inner lining of blood vessels), dysfunction of which can be associated with inflammation that is found in a subgroup of patients.
  • These microRNAs may therefore provide biomarkers and help further characterise endothelial dysfunction in ME/CFS.
Austria team
Dr Monika Riederer, Dr Francisco Westermeier and Dr Jennifer Blauensteiner

Summary

Some of the first research supported by the nascent ME Research UK more than twenty years ago was conducted by a team at the University of Dundee looking at blood-vessel function and the endothelium in people with ME/CFS.

So, since this is an area in which we have a long-established interest, we were keen to support Dr Francisco Westermeier and his colleagues at FH Joanneum University of Applied Sciences in Austria in their plans to look at endothelial function in ME/CFS in more detail.

The first fruits of this research were published in the journal Scientific Reports earlier this year, in an article written by Dr Jennifer Blauensteiner.

Inflammation is part of the body’s defence mechanism and healing process, and involves an increase in blood flow to an injured area, in order to bring protective immune cells into the tissue to combat infection and repair damage.

But sometimes inflammation can persist for longer than required, or be triggered unnecessarily, and this may itself cause damage.

Inflammation appears to affect a subgroup of patients with ME/CFS, and has been implicated in other conditions affecting the cardiovascular system, particularly its impact on the endothelium.

The endothelium is a layer of cells lining every blood vessel, and is involved in controlling their opening and closing, and hence the amount of blood flowing through them.

One of the ways the endothelium controls blood flow is through the release of a chemical called nitric oxide.

Dr Blauensteiner used samples from the UK ME/CFS Biobank to look at a levels of circulating microRNAs, which are molecules that help cells control what proteins they make.

She found that levels of five of these microRNAs were increased in people with ME/CFS compared with control subjects. Furthermore, these five micro-RNAs are all involved in controlling the endothelium, specifically via the pathway that generates nitric oxide.

These findings provide more evidence of endothelial dysfunction as a significant factor in the pathology of ME/CFS, but also raise the possibility that these microRNAs may represent biomarkers to distinguish patient groups.

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.