by Queen Mary, University of London
Credit: Pixabay/CC0 Public Domain
Researchers from Queen Mary University of London have found that the molecule RvT4 enhances the body’s natural defenses against atherosclerosis (hardening of the arteries) in patients with rheumatoid arthritis.
Studies in mice undertaken by researchers from Queen Mary University of London’s William Harvey Research Institute and Center for Inflammation and Therapeutic Innovation show that increasing levels of the RvT4 molecule 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 could lead to better treatments for people who have rheumatoid arthritis (RA), and who are at higher risk of developing cardiovascular disease.
Rheumatoid arthritis (RA) is the most common form of inflammatory arthritis in the UK and affects around 1% of the population. Approximately 10,000 people receive a diagnosis of RA every year. Alongside the more widely-known symptoms of joint inflammation, people with the condition are also twice as likely as others to develop blood vessel disease. This can lead to serious complications and an increased risk of premature death.
One type of blood vessel disease seen in people with RA is atherosclerosis, which is caused by a build-up of fatty material called ‘plaque’ along the artery walls. This build-up causes the arteries to harden and narrow, making it more difficult to circulate blood around the body. These blockages can also break free, causing heart attacks and strokes. Understanding the reasons why RA patients are at increased risk of these cardiovascular problems is critical in developing better treatments for this group and others.
To gain a better understanding of the causes of blood vessel disease in patients with RA, researchers explored the role of a group of molecules called 13-series resolvins (RvTs). In experimental arthritis the levels of one of these molecules, RvT4, are markedly reduced, a phenomenon that associates with a higher degree of blood vessel disease. This study was designed to explore why this might be the case.
Published in Nature Communications, the study found that treating arthritic mice with RvT4 reduced blood vessel inflammation by re-programming macrophages—a group of white blood cells that accumulate in the diseased vessels—to release stored lipids.
Researchers observed that these lipids were preventing the macrophage from carrying out their usual work of clearing dead cells and reducing localized inflammation in blood vessels. Once freed of their lipid burden, the macrophages were able to move and work much more effectively to reduce the causes of atherosclerosis. The observation that RvT4 restores protective macrophage biological activities is an exciting finding.
RA patients also often present with metabolic dysfunction and this is thought to exacerbate vascular disease. The study found that administration of RvT4 to mice engineered to develop characteristics of metabolic dysfunction, advanced atherosclerosis, and arthritis led to an overall decrease in lipoprotein-associated cholesterol in plasma and an increase in the ratio of HDL-associated cholesterol to total cholesterol.
More information: Resolvin T4 enhances macrophage cholesterol efflux to reduce vascular disease, Nature Communications (2024). DOI: 10.1038/s41467-024-44868-1
Journal information: Nature Communications
Provided by Queen Mary, University of London
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