Heart disease remains the leading cause of death in the United States, even with decades of effort focused on controlling risk factors like diabetes, high blood pressure, and high cholesterol.
Despite the use of medications such as aspirin and statins, many people still experience heart attacks and strokes.
Now, scientists at the University of Michigan may have found a missing piece of the puzzle: a protein called suPAR, produced by the immune system, which could be a key driver of atherosclerosis—the hardening and narrowing of arteries that leads to cardiovascular disease.
Atherosclerosis affects over a billion people worldwide and is a major cause of heart attacks and strokes. SuPAR, or soluble urokinase plasminogen activator receptor, is made in the bone marrow and helps regulate immune system activity.
While high suPAR levels have long been associated with heart disease, this new study shows for the first time that elevated suPAR levels can directly cause atherosclerosis.
The researchers analyzed data from over 5,000 people without any history of heart disease and found that those with higher suPAR levels were far more likely to develop atherosclerosis, regardless of other risk factors such as high cholesterol or high blood pressure.
This suggested that suPAR might be an independent cause of cardiovascular disease.
To better understand the link, the scientists conducted a genetic study involving 24,000 people. They identified a specific genetic variant in the PLAUR gene, which controls suPAR production.
People with this variant had higher suPAR levels in their blood and were significantly more likely to develop atherosclerosis.
The connection was confirmed through advanced genetic analysis of 500,000 participants in the UK Biobank and replicated in two other large datasets, strengthening the evidence that suPAR plays a direct role in causing atherosclerosis.
To further validate their findings, the researchers conducted experiments on mice. Mice with elevated suPAR levels developed more atherosclerotic plaques in their arteries compared to mice with normal suPAR levels.
These plaques can block blood flow and lead to heart attacks or strokes. The experiments confirmed that high suPAR levels are not just a marker of disease but a cause.
This discovery has the potential to revolutionize how heart disease is treated. Traditional therapies like cholesterol-lowering drugs target well-known risk factors but have no effect on suPAR levels.
The research team, led by Dr. Salim Hayek, is now working on developing treatments to safely reduce suPAR levels as a new strategy for preventing and treating cardiovascular disease.
The study also sheds light on the connection between heart disease and kidney disease, which are often linked. About two-thirds of people with kidney disease also have cardiovascular disease, and over 40% of heart disease patients show signs of kidney problems.
High suPAR levels may be a common factor contributing to both conditions, offering a new explanation for this overlap.
Published in the Journal of Clinical Investigation, the findings could lead to a major shift in how we approach cardiovascular disease. By targeting suPAR, doctors might be able to prevent atherosclerosis and reduce the risk of heart attacks and strokes, offering new hope to millions of patients.
This breakthrough highlights the importance of continuing research into the immune system’s role in chronic diseases and could pave the way for more effective, personalized treatments for heart disease.
If you care about heart health, please read studies about top 10 foods for a healthy heart, and how to eat right for heart rhythm disorders.
For more health information, please see recent studies about how to eat your way to cleaner arteries, and salt and heart health: does less really mean more?
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