Nijmegen – Arteriosclerosis causes heart and cerebral strokes. Researchers at Radboudumc have discovered that the protein prosaposin plays an important role in arteriosclerosis. This was unknown until now. “Prosaposin may be a new target for the treatment of atherosclerosis,” they write in a publication in Science Translational Medicine.
Arteriosclerosis, also called atherosclerosis, is a disease of the blood vessels that causes heart and cerebral strokes. It arises because cholesterol accumulates in the vessel wall and causes a chronic inflammatory reaction there. Cholesterol-lowering drugs can inhibit arteriosclerosis. Recent research has shown that it can also prevent heart attacks and strokes. The challenge is to inhibit the inflammation of the vascular wall as specifically as possible, without hampering the defenses in the rest of the body that protect us against infections.
Increase energy consumption
“The cells responsible for inflammation in arteriosclerosis are macrophages. This inflammatory process takes a lot of energy. The cells therefore have to increase their energy consumption considerably. Unraveling this process is important. This not only provides insight into the inflammatory activity – and thus arteriosclerosis – that is structured. It may also provide leads for slowing down that process, ”say the researchers.
Turn off the power
An international team of researchers, led by Raphaël Duivenvoorden of Radboudumc, has investigated what happens when you ‘switch off the power’ of the macrophages. The main switch of the energy system is a protein complex called mTOR. Using nanotechnology, they were able to turn off this main switch specifically in macrophages. They then investigated the effect of this on arteriosclerosis in a mouse model. Duivenvoorden: “After one week of treatment, we saw that the arteriosclerosis and the associated inflammation decreased.”
New role of prosaposin discovered
They then went on to unravel the molecular mechanism underlying this powerful anti-inflammatory effect. One protein always emerged, the protein prosaposin. Its role in arteriosclerosis was unknown. Duivenvoorden: “In additional experiments we found that prosaposin has an important effect on the energy balance of macrophages. Mice that cannot produce prosaposin also developed less arteriosclerosis and vascular wall inflammation. ”
Prosaposin and atherosclerosis in humans
The researchers then wanted to know whether prosaposin also plays a role in arteriosclerosis in humans. Duivenvoorden: “We saw that a lot of prosaposin was produced by macrophages and that this is related to their inflammatory activity. It confirms that in macrophages prosaposin plays a key role in arteriosclerosis. This makes it a new potential target for the treatment of atherosclerosis. ”
Watch the video about this research here: https://www.youtube.com/watch?v=b6955nNbgkY
–
