Atherosclerosis is a disease in which fatty plaques accumulate in the arteries and increase the risk of heart disease or stroke,media reported. But now, researchers from Oxford University have found a protein that appears to trigger this chain of events, and drugs against it may yield new ways to prevent these deadly build-ups.
Many people, especially those who smoke or eat high-fat foods, have their arteries damaged over time. Areas of arteries that bend or branch are more susceptible to chronic inflammation, which affects blood flow and causes plaque formation in the area. This, in turn, further restricts blood flow and eventually leads to heart disease and stroke.
Scientists don’t yet know how all the debris in the process is grouped together, but it appears that some molecules act as “mechanical sensors.” Now, a team of researchers at the University of Oxford has found that a mechanical protein called Plexin D1 appears to have a strong relationship with plaque formation.
“We pulled up the Plexin D1 protein with very tiny magnetic tweezers, and we found that it responded to the pull by releasing signals that began with a domino effect and eventually led to plaques that could lead to heart attacks,” said Ellie Tzima, lead researcher on the study.
The team tested the role of the protein in mice and found that it could fold itself into two main shapes — a closed ring and an open “chair-like” one. And importantly, different shapes behave differently, with only chair-shaped proteins reacting to tweezers, while ring proteins do not.
To do this, the researchers designed cells containing only the ring-shaped Plexin D1, which, if yes, did not respond to blood flow interference and therefore did not trigger the process that caused plaque build-up. The team then took the same step in mice by genetically editing it to have only ring-shaped Plexin D1, which had far fewer arterial plaques even when they were fed high-fat foods.
While the discovery of the protein and mechanism sits not yet directly in humans, the team says it sheds light on an important new target that could help develop drugs to prevent atherosclerosis in the future.
Tzima says they are now sifting through the drug bank to find a drug that blocks only the chair-shaped Plexin D1 so they can block the plaques before they form.