For decades, doctors have tried to fight heart disease by focusing on the main risk factors — controlling diabetes, lowering blood pressure, and reducing cholesterol with medications like aspirin and statins.
While these treatments help, heart disease remains the leading cause of death in the United States, and many people still suffer heart attacks even after managing these risks.
Now, researchers at the University of Michigan have discovered another possible reason why heart disease continues to be such a big problem.
They found that a protein made by the immune system, called soluble urokinase plasminogen activator receptor (suPAR), can actually cause atherosclerosis. Atherosclerosis is a condition where the arteries become hard and narrow, which can lead to heart attacks and strokes. It affects more than a billion people worldwide.
SuPAR is produced in the bone marrow and acts like a thermostat for the immune system, controlling how active it is. While doctors already knew that high levels of suPAR were linked to heart disease, this study is the first to prove that high suPAR levels can directly cause atherosclerosis.
The researchers looked at data from over 5,000 people with no known heart disease. They found that people with higher suPAR levels were much more likely to develop atherosclerosis and suffer serious heart problems — even if they didn’t have other common risk factors like high cholesterol or high blood pressure.
To better understand the connection, the team analyzed genetic data from 24,000 people. They discovered a genetic variant in a gene called PLAUR, which controls suPAR production. People with this variant had higher suPAR levels in their blood, and this genetic trait was strongly linked to atherosclerosis.
The researchers confirmed the cause-and-effect relationship using a method called Mendelian randomization, which uses genetic information to study health outcomes. They analyzed data from 500,000 participants in the UK Biobank and replicated the results in two other large datasets.
The team also tested the theory in mice. Mice with high suPAR levels developed many more atherosclerotic plaques in their aortas — the main arteries that carry blood from the heart — compared to mice with normal suPAR levels.
This lab evidence, combined with the human genetic and clinical data, strongly supports the idea that suPAR is a direct cause of atherosclerosis.
This discovery is important because current treatments for atherosclerosis, like cholesterol-lowering drugs, don’t affect suPAR levels. The researchers are now working on ways to safely lower suPAR as a new strategy for preventing and treating heart disease.
The findings are also connected to kidney disease, which affects about one in seven Americans. Many people with kidney disease also have heart disease — in fact, two-thirds of kidney patients also have cardiovascular problems, and over 40% of heart patients show signs of kidney disease.
The study, led by Dr. Salim Hayek and published in the Journal of Clinical Investigation, could lead to a major change in how heart disease is treated. If researchers can find a safe way to lower suPAR, it could offer new hope to millions of people at risk of heart attacks and strokes.
If you care about heart health, please read studies about root cause of heart rhythm disorders and Warning signal from the kidneys can predict future heart failure risk.
For more information about heart health, please read studies about a surprising link between alcohol drinking and heart health and both blood pressure numbers can predict heart disease risk.
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