Science
First responder protein triggers heart attack-causing plaques
Changes to a protein that detects turbulent blood flow could prevent life-threatening plaques from forming, according to research we part-funded.
Researchers from University of Oxford have found that a protein called Plexin D1 senses disturbances in the flow of blood in arteries. This causes a string of events which lead to inflammation and the build-up of fatty plaques - the underlying cause of devastating heart attack and strokes.
Professor Metin Avkiran, our Associate Medical Director, said:
“Understanding how and why these plaques develop in particular areas of arteries has been a longstanding challenge for scientists. This groundbreaking study has identified a protein that may be the key sensor that triggers the whole disease process.”
Professor Ellie Tzima and her team found that Plexin D1 can fold into three different shapes - closed, ring-like, or an open, chair-like shape. They used small magnetic ‘tweezers’ to pull on the protein to mimic a disturbance and the protein only responded to this force when it was in its chair-like shape.
Using genetically engineered cells which only had the ring-shaped protein, they found that Plexin D1 did not respond to disturbed flow and did not activate the pathways that eventually lead to plaques. Similarly, these fatty plaques did not form in mice which did not have the Plexin D1 protein.
Drugs to prevent atherosclerosis
The team are now looking to find drugs that can block this blood flow-sensing protein when it is in the plaque-forming shape.
Professor Metin Avkiran added: “The very exciting possibility is that new drugs may be developed to target that protein, in order to prevent atherosclerosis developing in the first place - which could ultimately reduce the number of people affected by the world’s biggest killers."
The study was also funded by Wellcome Trust, National Institutes of Health and the University of Oxford.