Researchers have discovered a possible link between the excess production of inflammatory proteins that cause rheumatoid arthritis (RA) and the development of heart valve disease, including aneurysms.
The study was published in Proceedings of the National Academy of Sciences of the United States, according to a news release from Walter+Eliza Hall Institute of Medical Research.
Per the release, in many people with RA, their bodies produce too much of the inflammatory protein tumor necrosis factor (TNF), which recruits immune cells that damage the joints and keep the body in a perpetual state of inflammation.
The link between TNF overproduction and the development of RA has been known for many years, the release continues.
Yet, the research team, led by Walter and Eliza Hall Institute researcher Philippe Bouillet, PhD, identified critical regions of the DNA that control production of TNF, the release explains.
“We have identified a previously unknown way that the body destabilizes the molecules during the process of TNF production to stop too much of the protein being made. We could essentially develop agents that put a spanner in the works, stopping the factory production of TNF,” Bouillet states in the release.
Bouillet notes in the release that treating RA patients with drugs that “mop up” excess TNF has been very effective in managing the disease, but up to 50% of patients become unresponsive to the anti-TNF drugs because their bodies develop immunity to them.
However, he continues, he believes that targeting the regions of the DNA that destabilize the molecule could be an innovative way to interfere with protein production to dampen the amount of TNF being made.
According to the study, the existing drugs that “mop-up” excess TNF could help in treating inflammatory diseases affecting heart valves.
“This is the first time that we have linked the overproduction of TNF to heart valve disease,” Bouillet says in the release. “While it seems that genetics makes a substantial difference to the severity of the heart disease in our models, it does suggest that in humans we may be able to better diagnose heart valve disease in people with rheumatoid arthritis in the future.”
Bouillet also states in the release that existing drugs that block and remove TNF could be investigated for treating heart valve diseases.
“Clinicians have trialed drugs that target TNF in the past, but for diseases of the heart muscle and with poor effect,” he says in the release.
“Our studies suggest that excessive TNF drives heart valve—rather than heart muscle—diseases, and may be worth investigating for inflammatory diseases affecting the heart valves, such as rheumatic heart disease,” he continues in the release.
[Source: Walter+Eliza Hall Institute of Medical Research]
Philippe Bouillet, PhD (left) and Dr Derek Lacey (right) have identified an inflammatory link between rheumatoid arthritis and heart valve diseases. (Photo courtesy of Walter+Eliza Hall Institute of Medical Research)