For many years, doctors have battled cardiovascular disease by focusing on controlling diabetes, lowering blood pressure, and reducing cholesterol with medications like aspirin and statins.
Despite these efforts, heart disease remains the leading cause of death in the United States, with many people still suffering heart attacks even after managing these risk factors.
A recent breakthrough from scientists at the University of Michigan has uncovered a new culprit that might explain why heart disease persists despite traditional treatments.
The study revealed that a protein produced by the immune system, known as soluble urokinase plasminogen activator receptor, or suPAR, plays a significant role in causing atherosclerosis, a condition where the arteries harden and narrow, leading to heart disease.
Atherosclerosis affects over a billion people worldwide and is a major cause of heart attacks and strokes.
SuPAR is produced by the bone marrow and acts as a kind of immune system regulator, controlling the activity of the immune system like a thermostat.
Previously, high levels of suPAR were known to be associated with cardiovascular disease, but this study is the first to show that suPAR can actually cause atherosclerosis when its levels are elevated.
In their research, the team analyzed data from over 5,000 people who did not have any known heart disease.
They discovered that individuals with higher levels of suPAR were much more likely to develop atherosclerosis and experience serious cardiovascular events, regardless of other risk factors like high blood pressure or high cholesterol.
To dig deeper, the scientists conducted a genetic study involving 24,000 people to see if certain genetic variations were linked to higher suPAR levels in the blood.
They found a specific genetic variant in the gene called PLAUR, which is responsible for producing suPAR. People with this variant tended to have higher levels of suPAR in their blood.
Most importantly, the researchers discovered that this genetic variant was strongly linked to atherosclerosis.
They confirmed this connection through a Mendelian randomization analysis—a method that uses genetic information to understand the cause-and-effect relationship—of 500,000 participants in the UK Biobank.
The findings were also replicated in two other large datasets, further solidifying the evidence that high suPAR levels can cause atherosclerosis.
In addition to these human studies, the researchers conducted experiments on mice.
They found that mice with elevated suPAR levels developed significantly more atherosclerotic plaques in their aortas—the large arteries that carry blood from the heart to the rest of the body—compared to mice with normal suPAR levels.
This experimental data, combined with the clinical and genetic evidence, makes a compelling case that suPAR is a direct cause of atherosclerosis.
What makes this discovery particularly exciting is that it opens the door to new treatments for heart disease. Traditional therapies for atherosclerosis, such as cholesterol-lowering drugs, have no impact on suPAR levels.
The research team is now focused on developing treatments that can safely reduce suPAR levels as a new strategy to prevent and treat heart disease.
This study also ties into previous findings that link suPAR to kidney disease, which affects about one in seven Americans.
It’s common for people to have both conditions: two-thirds of those with kidney disease also suffer from cardiovascular disease, and over 40% of cardiovascular patients show signs of kidney disease.
The research, led by Dr. Salim Hayek and published in the Journal of Clinical Investigation, could lead to a major shift in how we approach the treatment of cardiovascular disease, offering new hope for millions of patients who continue to battle this deadly condition.
If you care about heart health, please read studies about how drinking milk affects risks of heart disease , and herbal supplements could harm your heart rhythm.
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