Molecule RvT4 Shows Promise in Reversing Arterial Blockages in Rheumatoid Arthritis Patients

Researchers from Queen Mary University Uncover Potential Treatment for Cardiovascular Complications in Rheumatoid Arthritis

London, February 6, 2024 – In a significant breakthrough, researchers from Queen Mary University of London’s William Harvey Research Institute and Center for Inflammation and Therapeutic Innovation have identified a promising molecule, RvT4, that enhances the body’s natural defenses against atherosclerosis in patients with rheumatoid arthritis (RA). The study, published in Nature Communications, unveils a potential therapeutic avenue to address cardiovascular complications in individuals with RA.

Key Findings:

1. Correlation with Atherosclerosis: The study reveals that plasma concentrations of 13-series resolvin (RvT)4 negatively correlate with vascular lipid load in mouse inflammatory arthritis, suggesting a potential link to atherosclerosis.
2. Mechanism of Action: Administering RvT4 to male arthritic mice on an atherogenic diet significantly reduces atherosclerosis. RvT4 activates cholesterol efflux in lipid-laden macrophages through a Scavenger Receptor class B type 1 (SR-BI)-Neutral Cholesterol Ester Hydrolase-dependent pathway, leading to the reprogramming of lipid-laden macrophages for tissue protection.
3. Macrophage Reprogramming: The study demonstrates that RvT4 reprograms macrophages, enhancing their ability to reduce local inflammation and remove blockages in blood vessels.
4. Vasculo-protective Activities: Pharmacological inhibition or knockdown of macrophage SR-BI reverses the vasculo-protective activities of RvT4 in vitro and in male mice in vivo.
5. Reducing Lipid Burden: RvT4 treatment releases stored lipids in macrophages, allowing them to carry out their usual functions of clearing dead cells and reducing localized inflammation in blood vessels.
6. Potential Therapeutic Target: The findings suggest that RvT4 could serve as a therapeutic target to mitigate atherosclerosis and associated cardiovascular complications in patients with RA.

Clinical Implications:

Rheumatoid arthritis patients, who are at an elevated risk of developing cardiovascular diseases, may benefit from targeted treatments focusing on RvT4 to address arterial blockages and reduce the risk of serious complications such as heart attacks and strokes. The research opens new avenues for developing interventions that go beyond traditional approaches to enhance the body’s natural defense mechanisms against atherosclerosis in this patient population.

As further research unfolds, the potential for RvT4-based treatments holds promise for improving the cardiovascular outcomes and overall quality of life for individuals with rheumatoid arthritis.

More information: Resolvin T4 enhances macrophage cholesterol efflux to reduce vascular disease, Nature Communications (2024). DOI: 10.1038/s41467-024-44868-1