Stiff vessels, kidneys, inflammation and a little bit of genetic material
New research reveals how a small piece of genetic material called a micro-RNA might explain why high blood pressure develops and how we might treat it.
Over a billion people around the world have high blood pressure, or hypertension, and it is one of the main reasons why people die before their time. Along with diabetes, high blood pressure is also the main cause of chronic kidney disease (CKD) and kidney failure. People with kidney failure will only survive if they have dialysis or a kidney transplant.
New research by scientists in Scotland has revealed a small piece of genetic material called a micro-RNA could explain why high blood pressure accelerates blood vessel ageing and reveals new potential ways to diagnose or treat it.
Stiff vessels and hypertension
As you get older, the walls of your arteries – the blood vessels taking blood from your heart to the rest of your body – get increasingly stiff. This so-called ‘arterial stiffening’ is a classic hallmark of high blood pressure and accelerated blood vessel ageing. But high blood pressure itself, along with diseases like diabetes and CKD, can also cause stiffness. If we can predict and understand how arteries become stiff, it might reveal how to tackle stiffening and lower blood pressure. This could benefit patients with CKD and heart disease.
Micro-RNAs – a signpost for stiff arteries
DNA is the master code (written in the language of genes) that is tightly curled up in the central hub, or nucleus, of almost every cell. RNA is made of shorter copies of bits of this DNA code, that a cell makes proteins from – and these proteins make up all the components of cells and tissues. Micro RNAs, or miRs, are tiny pieces of RNA that don’t carry clear instructions for the cell to make things from, but instead switch other genes on and off.
Biomarkers are molecular signposts or ‘flags’ in bodily fluids that indicate someone might have a disease. If miRs are detected in patient blood samples, they could act as a biomarker for artery stiffening.
There are hundreds of miRs in the body. But the researchers have found that one in particular, called miR-214, crops up in white blood cells called T-cells in fatty tissue around stiff arteries in those with high blood pressure.
One of the authors on this latest paper, Dr Laura Denby, who is a Kidney Research UK Senior Fellow at the University of Glasgow, had already found that miR-214 causes kidney scarring, or fibrosis following injury. In this latest paper partly funded by Kidney Research UK, Laura, together with a team of researchers led by Professor Tomasz Guzik and Dr Ryszard Nosalski at the University of Glasgow, wanted to find out if miR-214 was involved in high blood pressure and could explain why arteries become stiff.
Is our immune system the culprit?
Our immune system protects us from disease and infection every day. But sometimes it can go wrong and switch on things it shouldn’t, causing more harm than good.
The research team showed that miR-214 can ‘switch on’ T-cells in our immune system so they move into the fatty tissue around the arteries. Once in this tissue, those T-cells release a number of pro-inflammatory molecules called cytokines that cause inflammation and lead to arterial stiffening. This stiffening happens because the cytokines released by the T-cells activate cells called fibroblasts, which start to produce tough collagen fibres causing a scar, which makes the arteries less elastic.
But it doesn’t stop there. The same cytokines released by T-cells, affected by higher levels of miR-214, contribute to a process called oxidative stress. During oxidative stress, oxygen molecules that are extremely reactive damage the cells and the tissue lining, which also make the arteries stiffer.
Together, this work is the first to link a cascade of damaging events caused by the higher levels of miR-214 in activated T-cells, which lead inflammation and scarring around the arteries in people with high blood pressure.
What comes next?
This fascinating work suggests miR-214 is important in accelerated blood vessel ageing, caused by hypertension, and suggests targeting this molecule could be a way to combat artery inflammation and stiffening. Ultimately, it could mean patients get the right treatment quicker, offering hope to diseases like CKD where high blood pressure plays a key role.
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