Research suggests potential new strategies for fighting age-related vascular disease

Declining function of cells that help repair the inner lining of blood vessels, known as endothelial progenitor cells, rather than a dwindling supply of the cells, may underlie the increased risk of atherosclerosis and other vascular diseases as people grow older, according to a new study (PDF) in the May 3, 2005, issue of the Journal of the American College of Cardiology.

“Potentially, progenitor cell dysfunction may be a therapeutic target for the treatment of endothelial dysfunction and serve as a bioassay to determine endothelial function. In the general context of autologous cell based therapies, functional deficits should be taken into consideration,” said Christoph Kalka, M.D., at the Heinrich-Heine-University in Düsseldorf, Germany.

The endothelium is the elastic inner lining of blood vessels. Declining function of the endothelium is related to atherosclerosis, blood vessel inflammation, and blood clots that may trigger heart attacks or strokes. Endothelial progenitor cells appear to be essential to repairing damage from high cholesterol, high blood pressure and other sources of chronic injury.

“Potentially, endothelial progenitor cells are necessary to maintain healthy vessels and to prevent arteriosclerosis,” Dr. Kalka said.

Blood vessel problems increase as people get older, so the researchers wondered whether part of the explanation might be that either the number of repair cells declines or the individual cells become less effective.

“This is the first study to investigate functional features of circulating endothelial progenitor cells in healthy young and old volunteers without major cardiovascular risk factors, such as smoking, hypertension, high cholesterol, or diabetes,” lead author Christian Heiss, M.D., said.

They compared 20 young, healthy participants (average age 25) to 20 older, healthy individuals (average age 61). The subjects were tested for how well blood vessels in their arms reacted to sudden changes in blood flow when a pressure cuff on the arm was released. The researchers tested blood samples from each subject, in order to see how many endothelial progenitor cells were present, and also how well those cells survived, grew, and moved in response to chemical cues.

As expected, the blood vessels in the older subjects did not respond as well as those of the younger subjects to changes in blood flow. Similarly, endothelial progenitor cells taken from older subjects did not function as well as those from younger subjects. However, the older subjects had just as many of the repair cells as the younger subjects.

The results suggest that future treatments should focus on both improving the function of blood vessel repair cells as well as trying to boost their numbers. But first, the researchers say, they need to identify the factors that determine how well endothelial progenitor cells function.

This study looked at only certain types of progenitor cells, so it remains to be determined whether these specific cells accurately reflect the behavior of all the cells involved in repairing the inner lining of blood vessels and helping with the growth of new blood vessels.

In an editorial in the journal, Pascal J. Goldschmidt-Clermont, M.D., F.A.C.C., and his co-authors at the Duke University Medical Center in Durham, North Carolina, wrote that atherosclerosis starts with the declining ability of aging humans to renew the cells lining blood vessels. He noted that the problem isn’t just that toxins and other stresses injure blood vessel linings that worsen with old age. Rather, an additional critical change occurs, which is the declining ability of the body to repair the damaged vessels. As a result, the blood vessels have a harder time maintaining homeostasis, that is, constant tissue stability that allows for adequate blood flow despite changes in heart rate, blood pressure and other factors.

“In this report by Heiss et al., the authors provide evidence that the maintenance of arterial homeostasis could be impaired by the obsolescence of the cells that are responsible, at least in part, for the repair of arteries, the endothelial progenitor cells. The report is also significant because it suggests that it is not the quantity aspect of these cells produced by the marrow that fails with age, but instead, the quality of the precursors that become limiting, thus leading to deficient repair, failure of cardiovascular homeostasis and consequent thromboembolic complications,” Dr. Goldschmidt-Clermont said.

The American College of Cardiology, a 31,000-member nonprofit professional medical society and teaching institution, is dedicated to fostering optimal cardiovascular care and disease prevention through professional education, promotion of research, leadership in the development of standards and guidelines, and the formulation of health care policy.

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