Over time, atherosclerosis, a disease that causes fatty plaques to build up in the arteries, limits the flow of oxygen-rich blood to vital organs. Often leading to a heart attack, stroke and even death, researchers at Oxford University have now found a protein that triggers this process.
Lifestyle choices from smoking to eating high-fat diets tend to damage blood vessels- with areas at which they bend or branch off becoming particularly vulnerable to chronic inflammation, and thus the build-up of plaques. These plaques then make cardiovascular events such as heart attacks and strokes more likely. Although known for some time, the reason why this happened was largely unknown. This has now changed however as new research has shown that a protein called Plexin D1, that detects disturbances in blood flow caused by damage to arteries, plays a key role in the formation of these plaques.
Ellie Tzima, lead author of the research said, “We used very tiny magnetic ‘tweezers’ to pull on the Plexin D1 protein, and we found that it responded to the pulling force by releasing signals that start a domino effect, ultimately resulting in plaque that can go on to cause a heart attack.”
While testing the protein's role in mice, Tzima and her team found that Plexin D1 tends to exist in two shapes: either a closed ring, or an open shape, similar to a right-angled flip phone. In particular, they found that its shape affects its behavior: while the right angled variety responded to the tweezers, the ring-shaped version ignored them.
To understand the implications of this finding, the researchers then engineered cells to only contain the ring-shaped Plexin D1. In the end, they found that these cells did not respond to changes in blood flow, and thus didn’t trigger plaque-building processes. They then engineered mice to have the same protein profile. In doing so, they found that even when blood flow was disturbed, their arteries accumulated far less plaque, even when consuming a diet high in fat.
Although this finding is not directly applicable to humans just yet, the researchers say that it nevertheless points towards a new target for drug development to tackle atherosclerosis. Tzima said, “We’re now screening drug libraries to try a drug that blocks only the chair-shaped Plexin D1, so that we can block plaques before they even start.”