Study finds a new way to fight heart disease

For decades, doctors have focused on reducing heart disease by managing diabetes, lowering blood pressure, and controlling cholesterol levels. Medications such as aspirin and statins have saved countless lives, yet heart disease remains the leading cause of death in the United States. Many patients continue to suffer heart attacks even when these traditional risk factors appear well controlled.

Researchers at the University of Michigan now believe they have uncovered a missing piece of the puzzle. Their work points to a protein known as suPAR—short for soluble urokinase plasminogen activator receptor—as a previously overlooked driver of heart disease.

SuPAR is produced by the immune system and plays a significant role in atherosclerosis, a condition in which arteries harden and narrow, increasing the risk of heart attacks and strokes. Atherosclerosis affects more than a billion people worldwide and has long been linked to factors such as high cholesterol and high blood pressure. The new findings show that suPAR can independently trigger the disease.

The protein originates in the bone marrow and helps regulate immune activity. When suPAR levels are high, the immune system remains chronically activated, leading to persistent inflammation. Over time, this inflammation damages artery walls and promotes the buildup of plaque, making blood vessels more likely to become blocked.

According to the researchers, this is the first study to demonstrate that suPAR is not merely associated with heart disease but can directly cause it when present at elevated levels.

To reach this conclusion, the team analyzed health data from more than 5,000 people who had no history of heart disease. They found that individuals with higher suPAR levels were significantly more likely to develop atherosclerosis, even when their blood pressure and cholesterol were within normal ranges.

The researchers also examined genetic data from 24,000 people and identified a gene called PLAUR that influences how much suPAR the body produces. Certain versions of this gene were linked to higher suPAR levels and an increased risk of heart disease.

To further confirm their findings, the scientists used Mendelian randomization—a powerful genetic analysis technique—on data from 500,000 people in the United Kingdom. This approach helped establish a clear cause-and-effect relationship between elevated suPAR levels and heart disease.

Animal studies supported the results. Mice with increased suPAR levels developed more severe arterial blockages than those with normal levels, providing direct evidence of the protein’s damaging effects on blood vessels.

The discovery is significant because current heart disease treatments do not target suPAR. Common cholesterol-lowering drugs, including statins, have no effect on the protein. Researchers are now working to develop new therapies that specifically reduce suPAR levels, offering hope to patients who remain at risk despite following standard medical treatments.

The study also sheds light on the connection between heart disease and kidney disease, conditions that often occur together. SuPAR has already been linked to kidney damage, and targeting it could potentially help treat both disorders.

Led by Dr. Salim Hayek and published in the Journal of Clinical Investigation, the research could reshape the future of heart disease treatment. By focusing on suPAR, scientists aim to develop more effective therapies to protect millions of people from heart attacks and strokes.