Deposits in arteries, also known as plaques, can narrow blood vessels, reduce blood flow and trigger heart attacks or strokes. An international research team led by the DZHK site in Munich and in collaboration with the University of Bern has investigated how changes in the vessel wall trigger this process. The study was published in Cardiovascular Research. The last author is Yvonne Döring, who works at the University Hospital of Munich and the University of Bern.
When vascular muscle cells lose their function
The walls of large arteries contain smooth muscle cells that control how wide or narrow a vessel is. These vascular muscle cells change early on in the disease process. They react more strongly to fats and inflammatory signals, lose their original function and take on characteristics of immune cells. In this way, they themselves contribute to the formation of deposits.
The study shows that this abnormal process accelerates when the ChemR23 receptor is missing: in mouse models, the deposits grew faster without it. The cells divided more frequently, absorbed more LDL cholesterol and released less of it.
Why ChemR23 declines early
ChemR23 decreases even before deposits become visible. Researchers see several possible triggers. Early inflammatory stimuli in the vessel wall can affect the vascular muscle cells. High LDL levels cause more LDL particles to penetrate the vessel wall, where they alter the behaviour of the cells. Flow conditions in the arteries can also put the cells under stress. These influences throw them off balance. A decrease in ChemR23 is therefore not only a consequence of the disease, but part of an early switch that promotes later deposits.
Human tissue samples confirm the results
Studies on arterial tissue from patients show the same pattern. Healthy vascular muscle cells carry a lot of ChemR23. As soon as they lose their original role and react more strongly to fats, the receptor decreases significantly. The findings from human tissue thus correspond to the results from animal models.
What happens when ChemR23 is inhibited or activated
Experiments with human vascular muscle cells showed that inhibition of ChemR23 exacerbates the malformation. The cells divided more rapidly, absorbed more LDL, released less excess fat and activated internal signalling pathways that further drive these changes.
When the receptor was activated, several of these effects were weakened. The study thus shows that ChemR23 keeps the cells stable and controls how they process fats. Intervening in this receptor could help keep them healthy for longer and slow down the early malformation process.
The study provides clarity in a previously contradictory field of research. Previous studies described ChemR23 as either pro-inflammatory or protective, depending on the tissue examined. The new study shows that the receptor plays a stabilising role in the vessel wall. The picture is clear for vascular muscle cells: ChemR23 supports their normal function. When it is absent, the cells lose their balance and themselves promote the build-up of deposits.
Original publication:
Evans BR et al. ChemR23 prevents phenotypic switching of vascular smooth muscle cells into macrophage-like foam cells in atherosclerosis. Cardiovascular Research, 2025
