New Insights When the Immune System Meets Atherosclerosis
Researchers from the University of Michigan Public Health are identifying an immune protein that appears to drive the development of atherosclerosis, the condition where arteries narrow due to cholesterol plaque buildup. The findings are described in a study published in the Journal of Clinical Research and reflect a growing understanding of how immune system activity influences cardiovascular risk.
Over recent years, scientists have increasingly connected immune system behavior with atherosclerosis, the leading contributor to cardiovascular disease worldwide. These connections help explain why some people develop artery blockages even when traditional risk factors are controlled and offer clues for new approaches to prevention and treatment.
In one analysis, researchers looked at data from more than 5,000 individuals who did not have cardiovascular disease at the outset. The study found a strong association between higher levels of suPAR, an immune-related protein, and an elevated risk of both atherosclerosis and broader cardiovascular disease. suPAR is produced in the bone marrow and functions as a regulator of immune responses, suggesting that its concentration could reflect or influence inflammatory processes involved in plaque formation.
Further exploration involved genetic data from about 24,000 people. The researchers identified a variant of the PLAUR gene that correlated with higher suPAR levels. Another prior study had linked this same gene variant to a greater likelihood of developing atherosclerosis. To test these relationships, scientists turned to animal models. Mice engineered to carry a defective PLAUR gene showed higher suPAR levels and developed more atherosclerotic plaques than their normal counterparts, providing a biological link between the gene, the immune protein, and disease progression.
Scientists propose that elevated suPAR may activate immune cells more aggressively, potentially amplifying inflammatory responses in the presence of high cholesterol. The goal is to translate these insights into therapies that reduce suPAR levels and dampen harmful immune activity. Researchers anticipate progress toward potential drug candidates within the next three to five years, with the aim of lowering cardiovascular risk by targeting this immune pathway alongside traditional risk factor management.
Today, cardiovascular care typically emphasizes controlling cholesterol, blood pressure, and blood sugar to reduce risk. Yet the underlying process of atherosclerosis remains a central driver of disease for billions of people. This evolving line of research underscores the importance of understanding how immune signaling interacts with metabolic factors to shape heart health and offers a path to more comprehensive prevention and treatment strategies.