New research on mice has shed light on how high blood pressure causes changes to arteries in the brain, a process that leads to vascular dementia. The research, led by University of Manchester scientists, funded by the British Heart Foundation and published today in the journal Proceedings of the National Academy of Sciences, [1] has uncovered a route to developing the first ever drug treatments for vascular dementia that directly target a cause of the condition.
High blood pressure is the main cause of vascular dementia, a condition characterised by poor blood flow to the brain. The reduced blood supply starves brain cells of nutrients and over time they become damaged and die. Symptoms of vascular dementia include loss of energy, lack of concentration and poor memory.
It's normal for the brain's arteries to narrow and widen in response to changes in blood pressure. However, consistently high blood pressure causes arteries to stay narrow and restrict the brain's blood supply. Until now, it was not known why.
The study, from researchers at the Geoffrey Jefferson Brain Research Centre at The University of Manchester, reveals that - in mice - high blood pressure disrupts messaging within artery cells in the brain. Messages that should tell the artery to dilate to allow more blood to flow through aren't able to reach their target, leaving arteries permanently constricted.
By identifying drugs that could restore this communication, the researchers hope to soon be able to improve blood supply to affected areas of the brain and slow the progression of vascular dementia.
Professor Adam Greenstein, a clinician scientist specialising in high blood pressure at the University of Manchester and one of the leaders of the research, said:
"By uncovering how high blood pressure causes arteries in the brain to remain constricted, our research reveals a new avenue for drug discovery that may help to find the first treatment for vascular dementia. Allowing blood to return as normal to damaged areas of the brain will crucial to stopping this devastating condition in its tracks.
"Any drugs that are discovered to improve brain blood supply may also be able to open a new line of attack in treating Alzheimer's disease, which causes very similar damage to blood vessels as vascular dementia. Drugs to restore healthy blood flow could make current treatments, which focus on removing harmful amyloid plaques in the brain, more effective."
Studying mice with high blood pressure, researchers identified that a protein called junctophilin-2 was damaged. In healthy mice, junctophilin-2 holds two cells structures closely together, helping to transmit messages that tell arteries to relax. But, when junctophilin-2 is damaged, this signalling is disrupted.
Professor Sir Nilesh Samani, Medical Director at the British Heart Foundation, who funded the research, said:
"Vascular dementia affects around 150,000 people in the UK, and this number is going up. There are no treatments to slow or stop the disease, but we know that high blood pressure is an important risk factor. The incurable symptoms are hugely distressing for patients and those close to them.
"This exciting research reveals a specific mechanism by which high blood pressure might increase the risk of vascular dementia. Pinpointing how arteries remain permanently narrowed in vascular dementia could lead to the development of new effective treatments, raising hope that there may soon be a way to prevent this illness from destroying more lives."
While the findings are yet to be confirmed in humans, the processes of blood vessel narrowing and widening are very similar in mice and humans. The researchers are now investigating drugs that could restore junctophilin-2 function, which they hope, in future will lead to human studies that aim to restore healthy brain blood flow in vascular dementia.
