Heart disease remains the leading cause of death in the United States, even after traditional treatments to control risk factors like diabetes, blood pressure, and cholesterol using medications like aspirin and statins.
However, a recent study from the University of Michigan has found a protein that could cause both atherosclerosis and kidney disease, offering new possibilities for treatments.
The protein is called soluble urokinase plasminogen activator receptor, or suPAR, and is produced by the bone marrow.
It acts as a regulator for the activity of the immune system, essentially acting as an “immunostat.”
Past studies have shown suPAR to be a marker of cardiovascular disease, but this study is the first to show that high levels of protein actually cause atherosclerosis, the hardening of arteries that affects over a billion people worldwide.
The team analyzed data from over 5,000 people without known heart disease and found that those with higher suPAR levels were more prone to developing atherosclerosis and experiencing cardiovascular events, regardless of their underlying risk factors.
They also conducted a genetic study of 24,000 people to find whether certain genetic variations affected suPAR levels in blood.
They discovered a specific variant in the gene PLAUR that codes for suPAR, and people with that genetic variant tended to have higher suPAR levels.
Importantly, that genetic variant was linked to atherosclerosis in a Mendelian randomization analysis of 500,000 participants in the UK Biobank, which was replicated in two other large data sets.
In mouse models with high suPAR levels, researchers saw a dramatic increase in atherosclerotic plaques of mouse aortas compared to mice with normal suPAR levels.
The team is now looking into developing treatments to safely reduce suPAR levels as a strategy to prevent and treat heart disease, especially since traditional therapies for atherosclerosis have no impact on suPAR.
The study also found that suPAR is a pathogenic factor that causes kidney disease, which impacts one in seven Americans.
People often experience both conditions together, as two-thirds of people with kidney disease are affected by cardiovascular disease, and over 40% of patients with cardiovascular disease have signs of kidney disease.
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The study was conducted by Salim Hayek et al and published in the Journal of Clinical Investigation.
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