Treatment to Reverse Arterial Blockages in Rheumatoid Arthritis

Researchers from Queen Mary University of London’s William Harvey Research Institute and Center for Inflammation and Therapeutic Innovation found that increasing RvT4 levels in the body improves the ability of the body’s own defense mechanisms (macrophages) to reduce local inflammation and remove blockages in blood vessels. This breakthrough in understanding the processes involved may lead to new treatments for persons with rheumatoid arthritis (RA), who are more likely to develop cardiovascular disease.

Rheumatoid arthritis (RA) is the most common kind of inflammatory arthritis in the UK, affecting approximately 1% of the population. Approximately 10,000 people are diagnosed with RA each year. Aside from the more well-known signs of joint inflammation, people with the disorder are twice as likely as others to develop blood vessel disease. This can result in major problems and an increased risk of premature death.

Atherosclerosis, a kind of blood vessel disease prevalent in persons with RA, is caused by the accumulation of fatty material known as ‘plaque’ along the arterial walls. This build-up hardens and narrows the arteries, making it more difficult to circulate blood throughout the body. These blockages can potentially become free, resulting in heart attacks and strokes. Understanding why RA patients are at a higher risk of these cardiovascular issues is crucial for creating better treatments for this population and others.

To better understand the reasons of blood vessel dysfunction in RA patients, researchers investigated the significance of a collection of molecules known as 13-series resolvins (RvTs). In experimental arthritis, one of these molecules, RvT4, is significantly diminished, which is associated with a higher degree of blood vessel damage. This study aimed to investigate why this would be the case.

The study, published in Nature Communications, discovered that treating arthritic mice with RvT4 reduced blood vessel inflammation by reprograming macrophages, a type of white blood cell that accumulates in damaged capillaries, to release accumulated lipids.

Researchers discovered that these lipids were inhibiting macrophages from performing their normal functions of removing dead cells and decreasing localized inflammation in blood arteries. Once relieved of their fatty burden, macrophages were able to migrate and act far more efficiently to combat the causes of atherosclerosis. The discovery that RvT4 restores protective macrophage biological functions is an intriguing development.

RA patients frequently report with metabolic dysfunction, which is likely to worsen vascular disease. The study discovered that administering RvT4 to mice engineered to develop metabolic dysfunction, advanced atherosclerosis, and arthritis reduced lipoprotein-associated cholesterol in plasma while increasing the ratio of HDL-associated cholesterol to total cholesterol.