Heart disease is still the leading cause of death in the United States, despite major improvements in prevention and treatment.
Doctors can lower well-known risks such as high blood pressure and high cholesterol, but heart attacks and strokes still occur in many people who receive treatment.
Researchers at the University of Michigan have identified another possible piece of the puzzle. Their work points to a protein called suPAR, which is produced by the immune system and may directly contribute to the buildup of harmful material inside arteries.
This buildup is known as atherosclerosis. It happens when fatty deposits and other material collect in artery walls, causing the arteries to become harder and narrower and making it more difficult for blood to flow normally.
Over time, these deposits can grow or break open and trigger a blood clot. If blood flow to the heart is blocked, a heart attack can occur, while a blockage affecting the brain can cause a stroke.
SuPAR is short for soluble urokinase plasminogen activator receptor. It is produced mainly by immune cells that begin in the bone marrow, and scientists have known for years that people with high levels of suPAR in their blood are more likely to have heart and kidney problems.
However, an association does not prove that something actually causes disease. The University of Michigan team therefore used several different approaches to investigate whether suPAR simply appears alongside heart disease or actively helps cause it.
First, the researchers studied information from more than 5,000 people who had no known heart disease when they entered the study. People with higher suPAR levels were more likely to develop atherosclerosis later, even after the researchers considered traditional risks such as cholesterol levels and high blood pressure.
The team then examined genetic information from about 24,000 people. They found a variation in a gene called PLAUR, which is involved in the production of suPAR, and people carrying this variation tended to have higher suPAR levels and a greater risk of atherosclerosis.
The scientists tested the genetic connection further using information from about 500,000 participants in the UK Biobank, a large research database containing health and genetic information. They also checked the finding in two other large groups of people, adding support to the idea that suPAR itself plays a role in artery disease.
Experiments in mice provided another important clue. Mice with unusually high suPAR levels developed more fatty plaques in their arteries than mice with normal levels, suggesting that the protein was not simply a warning sign but could actively promote the disease process.
The finding may help explain why current heart treatments cannot prevent every heart attack or stroke. Medicines such as statins are very effective at lowering cholesterol and reducing cardiovascular risk, but they do not specifically target suPAR.
The research team, led by Dr. Salim Hayek, is now interested in finding safe ways to lower suPAR. If future studies confirm that reducing the protein also reduces disease, suPAR could become a new treatment target used alongside existing approaches rather than replacing proven therapies.
SuPAR may also help scientists understand the close connection between heart and kidney disease. Problems in the two organs often occur together, and previous research has linked high suPAR levels with kidney damage as well as cardiovascular disease.
The study was published in the Journal of Clinical Investigation. The findings suggest that the immune system may have a larger role in atherosclerosis than previously recognized and could eventually lead to new ways to identify and treat people who remain at high risk despite controlling traditional heart disease factors.
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