More data on potential anti-aging cardiovascular benefits of blocking tumor necrosis factor alpha.

American Journal of Pathology - Recent studies show promise for significantly reducing vascular aging by inactivating TNFa, which has been linked to blood vessel dysfunction and cell death. The related report by Csiszar et al., “Vasculoprotective effects of anti-TNFa treatment in aging,” appears in the January 2006 issue of The American Journal of Pathology (Am J Pathol 2006 170: 388-398).

Age-related vascular diseases, including high blood pressure, heart attack and stroke, occur naturally, even in otherwise healthy individuals. Advanced age is also associated with increased levels of TNFa, a protein that can attack and destroy tumor cells but can also exacerbate chronic inflammatory diseases. To date, no studies have investigated the potential beneficial effects of TNFa inhibition in keeping blood vessels healthy during aging, making this the first study of its kind.

Csiszar and collegues treated aged rats with etanercept to test the hypothesis that anti-TNFa treatment protects vascular health in aging. Etanercept (Enbrel) is an FDA-approved drug that binds and inactivates circulating tumor necrosis factor alpha (TNFa). Recent studies have demonstrated that anti-TNFa therapies, including etanercept, may improve inflammation-related vascular disease, including heart failure.

Csiszar and colleagues made four notable findings in their study. First, they confirmed that in advanced aging, increased TNFa levels were associated with significant impairment of blood vessel relaxation, which is required for proper regulation of blood pressure.

Second, blocking TNFa via chronic etanercept treatment decreased cell death in aged blood vessels, demonstrating that increased TNFa levels likely contribute to age-related cardiovascular disease. Similar cell-protective effects were found when anti-TNFa antibodies were used in cell culture.

Third, not only was TNFa released into the blood, where it can have systemic effects, but it is also expressed within blood vessel walls, where it can exert specific local effects on the blood vessels and vascular enthothelium.

Lastly, administration of TNFa to young arteries reproduced the features of vascular aging, such as blood vessel dysfunction and cell death, further confirming the role of TNFa in the aging of endothelial cells and the cardiovascular system.

This work was supported by grants from the American Heart Association, American Health Assistance Foundation, American Federation for Aging Research and National Institutes of Health.

Editorial note:  In addition to the brand name drug Enbrel, another prescription medication (generic) called pentoxifylline has TNF-a inhibitory effects, and is already commonly prescribed for some circulatory conditions.  Also, the omega-3 fatty acid DHA in fish oil and the herb stinging nettles are said to have significant anti-TNF-alpha effects.  However, to my knowledge no direct comparison studies of TNFa inhibitory power are available between these two medications and the two supplements. It has also been suggested that TNFa inhibitors should be stopped when people develop infections, as tumor necrosis factor alpha is needed to fight off infections, but this subject should be discussed with your doctor if you are taking TNFa inhibitors for any reason. For basic information on pentoxifylline, visit this link to the Medline page for this medication for vascular disease and diabetic neuropathy with tumor necrosis factor alpha (TNFa) inhibition. - Dr. Z.

The knowledge that cardiovascular disease is the leading cause of death for both men and women in the U.S. underscores the significance of these findings. Anti-TNFa treatment could one day lead us closer to decreased inflammation and better blood vessel health and heart health as we age (Courtesy of EurekAlert!, a service of AAAS).