Role of Sirt1/NOS axis in vascular and immune homeostasis: a missing piece in the ME/CFS puzzle?

Principal Investigator

Dr Francisco Westermeier

Institution

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

Start date

September 2019

Background and aim

The immune system is a hot topic at the moment in ME research. Many studies in this area have been recently published or are ongoing, including four currently being funded by ME Research UK.

Dr Francisco Westermeier and his colleagues at FH Joanneum University of Applied Sciences in Graz, Austria are also exploring the potential impact of immune abnormalities in ME/CFS, in a project recently awarded funding by ME Research UK. But they are taking a slightly different tack.

Austria team
Dr Monika Riederer, Dr Francisco Westermeier and Dr Jennifer Blauensteiner

One consequence of an activated immune system is inflammation. This is part of the body’s defence mechanism and healing process, involving an increase in blood flow to an injured area, and the migration of 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 has been implicated in a number of conditions affecting the cardiovascular system (i.e. the heart and blood vessels), specifically its impact on the function of the endothelium. This is a layer of cells lining every blood vessel involved in controlling their opening and closing, and hence the amount of blood flowing through them.

Some of the first research supported by our charity was conducted by a team at the University of Dundee looking at endothelial function in people with ME/CFS.

One of the ways the endothelium controls blood flow is through the release of a chemical called nitric oxide. But nitric oxide is a double-edged sword – while it is essential in normal endothelial function (and is also involved in the central nervous system), too much can be damaging and lead to prolonged inflammation.

Dr Westermeier is exploring this complicated relationship in more detail by looking at whether the cellular mechanisms that control nitric oxide production are altered in ME/CFS.

Using blood samples obtained from the UK ME/CFS Biobank, he will assess levels of nitric oxide and the proteins involved in its production (Sirt1, eNOS and Arg1). He will also investigate whether this is altered in endothelial cells that have been exposed to blood plasma from people with ME/CFS.

The researchers hope their findings will throw new light onto the role of these complex mechanisms in ME/CFS, and possibly identify new biomarkers of endothelial dysfunction in the illness.

Dr Westermeier says that ME/CFS is “still poorly recognised in Austria, in part due to the lack of funding and research”. He hopes this project will also help raise awareness of the condition in his country.

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