Endothelial progenitor cells could serve as biological marker for cardiovascular disease

February 12, 2003

The number of circulating endothelial progenitor cells in an individual's blood -- the precursor cells to those that line the insides of blood vessels -- may be an indicator of overall cardiovascular health, according to research by scientists at the National Heart, Lung, and Blood Institute (NHLBI) and Emory University School of Medicine. The research was published in the Feb. 13 issue of the New England Journal of Medicine.

The endothelial cells lining the blood vessels provide essential communication between the vessels themselves and circulating blood cells, allowing the blood to flow smoothly. In diseases such as atherosclerosis, however, the endothelial layer becomes damaged and the vessels do not function efficiently. Until recently, scientists believed that nearby endothelial cells were recruited to help repair damaged blood vessels or form new ones to circumvent blocked vessels or to repair wounds. Evidence now shows, however, that endothelial progenitor cells, probably generated in the bone marrow, circulate in the bloodstream and are recruited to form new blood vessels or repair damaged ones.

The NHLBI and Emory scientists postulated that endothelial cells generated in the bone marrow contribute to continuous repair of the endothelial lining of blood vessels and that a lack of these cells can lead to vascular dysfunction and the progression of cardiovascular disease. They measured the number of "colony-forming units," or clumps, of endothelial progenitor cells in the peripheral blood of 45 men with a mean age of approximately 50 years. The men had various degrees of cardiovascular risk, but no history of cardiovascular disease. The researchers also measured blood vessel function using non-invasive high-resolution ultrasound of the brachial artery.

The research team calculated the subjects' risk for cardiovascular disease using the Framingham risk factor score, commonly used to predict the risk of coronary artery disease in individuals without clinical disease. They found a significant inverse correlation between the number of circulating endothelial progenitor cells and the Framingham risk factor score. They also found a significant inverse correlation between the brachial artery measurement of vascular function and the number of circulating endothelial progenitor cells. The correlation between the brachial measurement of vascular function and the number of endothelial cells was stronger than it was between brachial function and conventional risk factors.

In order to test their hypothesis that endothelial progenitor cells age prematurely in individuals with higher cardiovascular risk factors, the investigators studied endothelial progenitor cells from subjects with either high or low Framingham risk scores. After seven days in culture, a significantly higher number of cells from the high-risk subjects had characteristics of senescence, or aging.

"Cardiovascular health is dependent on the ability of the blood vessels to continually repair themselves," says Arshed Quyyumi, MD, professor of medicine at Emory University School of Medicine, formerly of the NHLBI, and a member of the research team. "Evidence has shown that cardiovascular risk factors ultimately lead to damage to the endothelial layer of blood vessels. We can now speculate that continuing exposure to cardiovascular risk factors not only damages the endothelial layer, but may also lead to the depletion of circulating endothelial progenitor cells. Thus, the net damage to blood vessels and hence the risk of developing atherosclerosis depends not only on the exposure to risk factors, but also on the ability of the bone marrow-derived stem cells of endothelial origin to repair the damage.

"We will need larger studies to determine a definite cause and effect relationship between a decrease in these cells and adverse cardiovascular events. Our study did demonstrate, however, a correlation between endothelial progenitor cells, cardiovascular risk factors, increased senescence of endothelial progenitor cells, or stem cells, and vascular function. We are hopeful that further research will show that endothelial progenitor cells are a useful marker for cardiovascular disease risk."

Other members of the research team included Jonathan M. Hill, MRCP, Gloria Zalos, RN, Julian P.J. Halcox, MRCP, William H. Schenke, BA, Myron A. Waclawiw, PhD and Toren Finkel, MD, PhD, all of the NHLBI. The research was funded by the National Institutes of Health.
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Emory University Health Sciences Center

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