Drug decreases blood vessel stiffness in older primates
A novel drug that breaks down vascular collagen bonds in the body significantly decreased the stiffness of blood vessels in older non-human primates, according to a study conducted by National Institute on Aging (NIA) scientists and others.* The finding suggests the medication could be a new treatment for high blood pressure, heart failure, and certain vascular complications of diabetes.
ALT-711 (Alteon, Ramsey, New Jersey), a thiazolium-based compound, snips bonds or crosslinks created in the arteries and other tissues when glucose attaches to collagen. Crosslinks are cable-like structures that inhibit the natural flexibility of collagen strands. They tend to proliferate with age. Crosslinks appear to toughen tissues and may cause some of the deterioration associated with aging and diabetes, such as elevated systolic blood pressure, hardened arteries, and impaired kidney function.
In the study, six rhesus monkeys received doses of ALT-711 every other day for three weeks. Six weeks after the last treatment, all of the vessel walls tested were more flexible, and the effect persisted for more than four months after final administration of the drug. Blood flow through the heart also increased and this improvement persisted for nearly 10 months after the treatments ended. No significant changes in body weight or routine chemical measurements were detected during the follow-up period. The finding was published in the January 30, 2001 issue of Proceedings of the National Academy of Sciences.
"Arterial stiffening is a major factor in many of the vascular diseases associated with advancing age," said Edward Lakatta, M.D., co-author of the study and chief of the NIA's Laboratory of Cardiovascular Sciences. "The significance of this drug is it alters the properties of the arterial wall and makes it easier for the heart to eject blood into the blood vessels. These results, coupled with prior studies in smaller animals, certainly suggest that ALT-711 may be a safe and efficacious approach to decreasing the impact of arterial stiffness on cardiovascular health. However, further research, including on-going studies in people, will be needed in order to confirm and extend these findings."
The research was a joint effort by the NIA and Alteon, Inc., as part of the Cooperative Research and Development Act. The National Institute on Aging, one of 25 Institutes that constitute the National Institutes of Health, leads Federal efforts to support and conduct basic, clinical, epidemiological, and social research on aging and the special needs of older people.
* P.V. Vaitkevicius, M. Lane, H. Spurgeon, D.K. Ingram, G. S. Roth, J.J. Egan, S. Vasan, D.R. Wagle, P. Ulrich, M. Brines, J.P. Wuerth, A. Cerami, and E.G. Lakatta, "A Novel Cross-link Breaker Has Sustained Effects On Arterial and Ventricular Properties In Older Rhesus Monkeys, Proceedings of the National Academy of Sciences , 98:3, pp. 1171-1175, 2001