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Decreased NO Production in Endothelial Cells Exposed to Plasma from ME/CFS Patients

About

Status:
Completed
Principal investigator:
Country:
Austria
Study start:
Not available
Completion (planned):
Not available
Last update:
2023-12-01

 

Research types:
Basic research
Research areas:
Cardiovascular system dysfunction
Interventions:
Not applicable
Priv. Sector Partner:
Sponsors:

Project description

In their previous work, Dr Westermeier’s group analysed blood samples from people with ME/CFS, and found increased levels of five microRNAs, all of which are involved in control of the vascular endothelium and the generation of nitric oxide (NO). The team has continued this work with a new article written by Dr Romina Bertinat (who is based at the University of Concepción in Chile) and published in the journal Vascular Pharmacology. And this time they have been looking more directly at the production of NO.

To recap, 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. This ensures an adequate supply of blood and oxygen to tissues throughout the body. An important way in which the endothelium regulates blood flow is through the release of NO. NO therefore plays a critical role in maintaining a healthy cardiovascular system, and decreased production of NO is a characteristic of many diseases, including hypertension, diabetes and heart failure. The aim of Dr Bertinat’s study was to investigate whether endothelial cells exposed to plasma from people with ME/CFS would be impaired in their ability to generate NO. (Plasma is the liquid portion of blood which carries red and white blood cells, and platelets.)

Endothelial cells were incubated with plasma from people with ME/CFS (obtained from the UK ME/CFS Biobank) or with plasma from healthy control subjects. The cells were then exposed to proteins that are known to stimulate the production of NO, including insulin, bradykinin, histamine and acetylcholine. Importantly, the endothelial cells exposed to ME/CFS plasma generated significantly less NO than did the ones exposed to healthy plasma, and this was the case for all four of the stimulatory proteins tested. Another important finding related to the enzyme responsible for producing NO in the endothelium. The activity of this enzyme (endothelial NO synthase) was also reduced in the presence of plasma from ME/CFS patients, raising the possibility that it may represent a target for treatment. There are still questions about how these findings relate to the symptoms of ME/CFS, and Dr Westermeier discusses these issues in a recent interview with CureME (the team that runs the UK ME/CFS Biobank). He suggests that impaired NO production might lead to defective vascular function following exercise, which could indicate a role for NO in post-exertional malaise. But NO is also involved in metabolism and the immune system, raising more intriguing possibilities. For now, the team plans to look at several other biochemical pathways and metabolites involved in NO production.

(Description adapted from project website: see link above)

Patient cohort

ME/CFS according to Centers for Disease Control and Prevention (CDC) or Canadian Consensus Criteria (CCC), compared with healthy controls.

Patients enrolled: 23

Age group: 19 - 58 years (Adults)

Research areas
2
Research types
2
Research networks
0
Working groups
1
People
4
Publications
1
Organisations
1