New research led by a team from the University of Michigan suggests an immune protein may be a major causal factor in atherosclerosis, the thickening of arteries in the heart.
“Targeting the immune component central to the development of atherosclerosis is the Holy Grail for the treatment of heart disease,” explained Salim Hayek, senior author on the new study “This is the first time that a component of the immune system is identified that meets all the requirements for being a promising treatment target for atherosclerosis.”
The new research focused on an immune protein called suPAR. The protein is produced by bone marrow and functions as a general regulator of immune system activity.
For years, researchers have known suPAR to be an effective immune activity biomarker.
High levels of suPAR have been associated with everything from cancer to diabetes but most recently the immune protein has been found to play a causal role in kidney disease.
Preclinical studies have found inhibiting suPAR can prevent, or even reverse, kidney injury, indicating the protein may be more pathogenically linked to disease than previously thought.
This new study set out to explore the potential for suPAR to be a causal agent in cardiovascular disease using three different approaches.
“High suPAR levels appear to activate the immune cells and prime them to overreact to the high cholesterol environment, causing these cells to enter the blood vessel wall and accelerate the development of atherosclerosis,” Tyrrell explained.
“Even prior to developing atherosclerosis, the mouse aortas with high suPAR levels contained more inflammatory white blood cells, and the immune cells circulating in blood were in an activated state, or ‘attack-mode.'”.
Inhibiting suPAR could plausibly decrease one’s risk of cardiovascular disease and there are therapies already in development trying to do exactly that.
Monoclonal antibodies and small molecule inhibitors targeting suPAR have shown promising results in preclinical studies focusing on kidney disease.
A blood treatment therapy called plasmapheresis has been seen to both reduce suPAR levels and stabilize serious kidney disease in human patients.