For decades, doctors have focused on controlling diabetes, lowering blood pressure, and reducing cholesterol to fight heart disease. Medications like aspirin and statins have helped, but despite these efforts, heart disease remains the leading cause of death in the United States. Many people still suffer heart attacks even when their risk factors are well managed.
Now, scientists at the University of Michigan have uncovered a new factor that may explain why heart disease continues to persist: a protein called suPAR (soluble urokinase plasminogen activator receptor).
This protein, produced by the immune system, plays a key role in atherosclerosis, a condition where the arteries harden and narrow, increasing the risk of heart attacks and strokes.
A Hidden Cause of Atherosclerosis
Atherosclerosis is one of the most common causes of heart disease, affecting over a billion people worldwide. It occurs when fatty deposits build up in the arteries, restricting blood flow and increasing the risk of serious heart problems.
Doctors have long known that high cholesterol and high blood pressure contribute to this condition, but this new study shows that suPAR can actually trigger it.
SuPAR is produced by the bone marrow and helps regulate the immune system. In people with high levels of suPAR, the immune system stays constantly activated, leading to inflammation. Chronic inflammation damages the arteries, making them more prone to plaque buildup and hardening.
Until now, researchers had only linked suPAR to cardiovascular disease, but this study is the first to show that it can actually cause atherosclerosis when its levels are too high.
Strong Evidence From Large Studies
To understand how suPAR affects heart health, researchers analyzed data from over 5,000 people with no history of heart disease. They found that those with higher suPAR levels were much more likely to develop atherosclerosis, even if their cholesterol and blood pressure were normal.
To strengthen their findings, they examined genetic data from 24,000 people and discovered that a specific gene, PLAUR, controls suPAR production. People with a certain variant of this gene had higher suPAR levels and a greater risk of developing atherosclerosis.
To confirm this connection, they performed a Mendelian randomization analysis—an advanced method that uses genetic data to determine cause-and-effect relationships—on 500,000 participants from the UK Biobank. The results showed that suPAR is not just linked to heart disease but is actually a direct cause of it.
Experiments in Mice Confirm the Findings
The researchers also conducted experiments on mice. They found that mice with high suPAR levels developed significantly more atherosclerotic plaques in their arteries compared to those with normal levels. This provided strong biological evidence that suPAR plays a direct role in artery damage.
A New Path for Heart Disease Treatment
The discovery of suPAR as a key cause of atherosclerosis is groundbreaking because traditional heart disease treatments do not target this protein. Cholesterol-lowering drugs, such as statins, have no effect on suPAR levels.
Now, researchers are working on ways to lower suPAR as a new strategy for preventing and treating heart disease. If successful, these treatments could help millions of people who still face heart problems despite following existing medical advice.
Connection Between Heart and Kidney Disease
This study also adds to growing evidence that suPAR plays a role in kidney disease. Kidney disease and heart disease often occur together—two-thirds of people with kidney disease also have heart disease, and 40% of heart patients show signs of kidney problems.
The discovery of suPAR’s role in both conditions may help doctors develop treatments that improve both heart and kidney health.
A Major Step Forward in Heart Disease Research
Led by Dr. Salim Hayek, this study was published in the Journal of Clinical Investigation and could lead to a major shift in how doctors treat heart disease. By focusing on suPAR, researchers hope to develop new therapies that go beyond traditional cholesterol and blood pressure management.
This breakthrough offers new hope for millions of people at risk of heart attacks and strokes, paving the way for more effective treatments in the future.
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