Atherosclerosis, the gradual buildup of fatty deposits inside arteries, remains one of the leading causes of heart attacks and strokes worldwide. While inflammation has long been recognized as a major contributor to the disease, new research from scientists at Ludwig Maximilian University of Munich suggests that certain inflammatory immune cells may also play a protective role in slowing its progression.
The study, recently published in the journal Circulation, investigated how different types of macrophages, immune cells responsible for clearing harmful substances from the body, affect the development of atherosclerotic plaques. These plaques form when fats such as cholesterol accumulate within artery walls, narrowing blood vessels and increasing the risk of cardiovascular events.
A Complex Role for Macrophages
Researchers used advanced four-dimensional microscopic imaging in mouse models to examine the behavior of macrophages within arterial plaques. Their findings revealed that macrophages without accumulated lipids, known as non-foamy or lipid-free macrophages, play a dual role in atherosclerosis.
On one hand, these cells help remove cellular debris and DNA released from dead cells, reducing the formation of cholesterol crystals that can destabilize plaques. On the other hand, they can also damage the endothelium, the protective inner lining of blood vessels, thereby contributing to inflammation.
The findings highlight the complexity of inflammatory processes in cardiovascular disease, showing that inflammation is not solely harmful but can also activate mechanisms that help control plaque growth.
miR-147 Emerges as a Potential Therapeutic Target
At the center of the study is a small regulatory RNA molecule called miR-147. Researchers found that miR-147 is predominantly produced by lipid-free macrophages and helps these cells efficiently clear dead cellular material while minimizing damage to blood vessel walls.
When miR-147 was absent, the researchers observed significantly greater plaque formation, increased accumulation of cellular debris, and higher levels of cholesterol crystals within arteries.
Further analysis showed that miR-147 suppresses the production of Galectin-3, a protein that can damage endothelial cells and interfere with the energy metabolism of macrophages. Reduced energy availability limits the cells' ability to clear debris, potentially accelerating plaque progression.
Implications for Future Cardiovascular Treatments
According to the research team, therapies designed to enhance or mimic miR-147 activity could offer a novel strategy for treating atherosclerosis. By selectively targeting harmful inflammatory pathways while preserving beneficial immune functions, such treatments may help reduce the risk of heart attack and stroke.
"The inflammatory response in atherosclerosis is complex and includes both harmful effects and mechanisms that limit plaque growth," the study authors noted, emphasizing that miR-147-based approaches may provide a new avenue for precision therapies aimed at cardiovascular disease.
The discovery adds to growing evidence that immune regulation plays a critical role in cardiovascular health and could pave the way for next-generation treatments focused on modifying inflammatory processes rather than simply lowering cholesterol levels.
