A new LMU study shows how immune cells differentially influence the formation of dangerous vascular deposits and identifies miR-147 as a potential starting point for future treatments.
The heart and brain depend on a continuous supply of oxygen. Even a short interruption in blood flow can have serious consequences, for example, if the blood vessels become narrowed or blocked by deposits.
Blood vessel branches are particularly vulnerable to such deposits. This is where fats such as cholesterol tend to accumulate on the blood vessel walls. The result is atherosclerosis, which gradually changes the arteries and increases the risk of heart attack and stroke.
The immune system is also involved in this process. Over many years, so-called macrophages (scavenger cells of the immune system) accumulate in the walls of blood vessels. They take in fat, accumulate it, and eventually die. What remains is cell debris and deposited fat, from which cholesterol crystals can form. These crystals destabilize plaques and promote thrombus formation, thereby increasing the risk of acute vascular occlusion.
Macrophages play a dual role
LMU researchers are currently investigating the role that different macrophages play in atherosclerotic plaques. Using four-dimensional microscopic images of mouse plaques, a team led by Professor Andreas Schober and Dr. Maliheh Nazari Jahantigh from LMU University Hospital showed that not only lipid-laden macrophages, but also lipid-free macrophages, play a crucial role in shaping the disease process.
These lipid-free macrophages serve a dual function. On the one hand, it removes cellular debris such as DNA from dead cells, thereby limiting the formation of cholesterol crystals. But it also attacks the endothelium, the thin cell layer that lines and protects blood vessels. Therefore, inflammation not only acts as a harmful force, but also partly as a limiting effect.
miR-147 as a potential therapeutic target
At the center of this balance is a small RNA molecule, miR-147. This microRNA is mainly produced in lipid-free macrophages. There, it helps cells remove dead cell debris while also limiting damage to the endothelium. In the absence of miR-147, plaque formation, DNA deposition from dead cells, and cholesterol crystals are all significantly increased.
According to the researchers, this effect is due to miR-147 suppressing the production of the protein galectin-3 in lipid-free macrophages. When galectin-3 is released, it not only damages endothelial cells but also interferes with the energy supply of macrophages. Without that energy, cells are slower at removing debris, and this process can further promote plaque formation.
The inflammatory response in atherosclerosis is complex and includes both deleterious effects and mechanisms that limit plaque growth. There is an opportunity for treatment here. miR-147-based therapy selectively affects the inflammatory process in atherosclerotic plaques and may reduce the risk of heart attack and stroke in the long term. ”
Dr. Nan Lee, lead author of the study
sauce:
Ludwig Maximilian University of Munich (LMU)
Reference magazines:
Lee, N. and others. (2026). mil 147 Limits the contribution of nonfoam macrophages to atherosclerosis. circulation. DOI: 10.1161/circulationaha.125.077821. https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.125.077821
