Scientists have discovered that, as far as arteries are concerned, inflammation can be both good and bad. In its well-known bad role, it can aid atherosclerosis, the plaque-forming process that clogs up arteries and raises the risk of heart attacks and strokes.
The study was done at the University of Virginia (UVA) at Charlottesville and now features in the journal Nature Medicine.
These findings have important implications for drugs that treat advanced atherosclerosis by reducing inflammation.
The investigators draw attention to the "high-profile drug" canakinumab, which is undergoing trials for the treatment of advanced atherosclerosis.
Based on their results, they suggest that, should it receive federal approval, the drug should only be given to "a select group of patients."
"What our data suggest," says senior study author Gary K. Owens, a professor of cardiovascular research at UVA, "is that you need to be extremely cautious in starting to give this drug more broadly to lower-risk patients."
"If you give it to the wrong person, it could do the opposite of what you intended," he warns.
Atherosclerosis and plaques
Most strokes and heart attacks are the result of the complex process of atherosclerosis.
The process builds up plaques in the inside walls of arteries, or blood vessels that supply the heart and other organs and tissues with oxygen and nutrients. The plaques are made of calcium, fats, cholesterol, and other bloodborne substances.
As atherosclerosis progresses, these plaques harden and cause the affected arteries to narrow and impede blood flow.
This increases the risk of heart attack if the artery nurtures heart muscle, or stroke if it is one that feeds the brain.
The traditional view is that the body deposits potentially harmful substances in the plaques and after this they do not change much and enter a dormant state. The "fibrous caps" that seal the plaques are thought to be inert, serving like patches on tires.
Plaque caps are constantly changing
By working with cell cultures and mice, however, Prof. Owens and his colleagues revealed that the caps are far from inert and can change rapidly and dramatically over time; they are constantly "remodeling."
They noticed that treatment with a drug that blocked an inflammation promoter weakened the cap structure, causing the plaque to rupture more readily.
The scientists suggest that reducing inflammation at the wrong time sends a signal that the job of sealing the plaque is done.
"This study," reports first author Ricky Baylis, who is a student in Prof. Owens's laboratory, "seems to indicate that the fibrous cap, as a structure, is actually much more plastic than previously thought."
Though at first this might appear to be a problem, Baylis says that it may actually present "a much greater opportunity to strengthen the caps to prevent heart attacks and strokes."
Prof. Owens reckons that studies similar to theirs should lead to better design of drugs that target the "bad parts of inflammation" while preserving and even promoting the "good parts" so as to "increase the stability of atherosclerotic lesions."
"[W]e believe our data suggest that if you suppress inflammatory response without first removing or reducing the cause of the inflammation [...] that this could become dangerous and have unintended consequences."
Prof. Gary K. Owens