Scientists have uncovered a previously hidden molecular trigger inside artery walls that may explain why some atherosclerotic plaques suddenly become dangerous, raising the risk of heart attacks and strokes.
In a study published in Precision Clinical Medicine, researchers from the Naval Medical University and partner institutions report that a key immune-related protein, interferon regulatory factor 7 (IRF7), acts as a switch that pushes artery smooth muscle cells into a harmful, inflammatory state. This shift weakens plaques and makes them more likely to rupture.
Atherosclerosis, long thought to be driven mainly by cholesterol buildup, is now understood as a chronic inflammatory disease. While immune cells such as macrophages have been the focus of most research, the new study highlights the active and decisive role of vascular smooth muscle cells—cells once considered largely structural.
Using single-cell RNA sequencing and lineage-tracing models, the team tracked how smooth muscle cells change during plaque development. Instead of following a single path, these cells split into multiple identities. One particular group became macrophage-like and highly inflammatory, expanding as the disease advanced.
Further analysis identified IRF7 as the master regulator behind this harmful transformation. When researchers selectively suppressed IRF7 in smooth muscle cells in mouse models, plaques became smaller and more stable. They showed less fat and dead tissue and developed thicker, collagen-rich fibrous caps—features associated with a lower risk of rupture.
Notably, these benefits occurred without changing blood cholesterol levels, pointing to a direct effect within the vessel wall itself. Data from human artery plaques supported the findings, revealing higher IRF7 activity in advanced and unstable lesions, closely linked to inflammation and immune cell buildup.
“Our findings challenge the traditional view that smooth muscle cells are passive players,” a senior author said. “Under IRF7’s control, they can actively drive inflammation and plaque vulnerability.”
Current treatments for atherosclerosis mainly target cholesterol, yet many patients remain at risk due to ongoing plaque inflammation. By identifying IRF7 as a central driver of harmful smooth muscle cell reprogramming, the study opens the door to new therapies aimed at stabilizing plaques from within the artery wall.
Targeting IRF7 or its downstream pathways could one day complement existing treatments, potentially reducing the residual risk of heart attack and stroke without interfering with lipid metabolism or essential immune functions.
