Endothelial Progenitor Cells Could Serve As Biological Marker for
Cardiovascular Risk
ATLANTA—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. |