Valhalla, NY -- 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 issue of The American Journal of Pathology.
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 vascular 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 exerts vasculoprotective effects in aging. Etanercept (Enbrel) is an FDA-approved drug that binds and inactivates circulating 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 vessel relaxation, which is required for proper regulation of blood pressure.
Second, blocking TNFa via chronic etanercept treatment decreased cell death in aged 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.
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 the cardiovascular system.
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. This treatment could one day lead us closer to better heart health as we age.
Written by Rachel J. Lowery.
This research was directed by Anna Csiszar M.D., Ph.D., and Zoltan Ungvari, M.D., Ph.D., of the Department of Physiology, New York Medical College, Valhalla, NY.
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.
Csiszar A, Labinskyy N, Smith K, Rivera A, Orosz Z, Ungvari Z. Vasculoprotective effects of anti-TNFa treatment in aging. Am J Pathol 2006 170: 388-398.
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The American Journal of Pathology, the official journal of the American Society for Investigative Pathology (ASIP), seeks to publish high-quality original papers on the cellular and molecular mechanisms of disease. The editors accept manuscripts which report important findings on disease pathogenesis or basic biological mechanisms that relate to disease, without preference for a specific method of analysis. High priority is given to studies on human disease and relevant experimental models using cellular, molecular, biological, animal, chemical and immunological approaches in conjunction with morphology.