<<http://news.mc.duke.edu/news/article.php?id=7451>>

Progenitor Cells Predict Heart Disease Severity

NEW ORLEANS -- Duke University Medical Center researchers have uncovered
a strong relationship between the severity of heart disease and the level
of endothelial progenitor cells circulating in the bloodstream. This
relationship, if confirmed by ongoing studies, could represent an
important new diagnostic and therapeutic target for the treatment of
coronary artery disease, they said. 

These endothelial progenitor cells (EPC) are produced in the bone marrow,
and one of their roles is to repair damage to the lining of blood
vessels. Duke cardiologists believe that one cause of coronary artery
disease is an increasing inability over time of these EPCs to keep up
with the damage caused to the arterial lining, or endothelium. 

"In our study we found that patients with multi-vessel disease had many
fewer EPCs, which supports our hypothesis that these cells play an
important role in protecting blood vessels," said cardiologist Geoffrey
Kunz, M.D., of the Duke Clinical Research Institute. "If you don't have
enough of the cells, the ongoing damage to the endothelium from
traditional risk factors occurs faster than the body's ability for
repair." 

Kunz presented the results of the Duke analysis March 9, 2004, at the
annual scientific sessions of the American College of Cardiology. 

In an article published last year in Circulation (July 29, 2003), Duke
researchers reported discovering in mouse studies that a major outcome of
aging is an unexpected failure of the bone marrow to produce EPCs needed
to repair and rejuvenate arteries exposed to a genetically induced risk
of high lipid levels. The researchers demonstrated that an age-related
loss of these particular cells is critical to determining the onset and
progression of atherosclerosis, which causes arteries to clog and become
less elastic. 

For the current study, the researchers measured the levels of EPCs in 122
patients undergoing diagnostic cardiac catheterization procedures at Duke
and correlated those findings with the severity of coronary artery
disease. Specifically, they determined how many of the coronary arteries
showed signs of atherosclerosis. 

The average age of the patient sample was 58, with 37 percent of them
having multi-vessel disease, 29 percent having diabetes and 20 percent
having had a recent heart attack. 

The researchers removed EPCs from the blood samples and grew them in cell
culture to determine how many of the cells would grow. The number of
cells is measured as colony-forming units (CFU). 

"We found that the patients with multi-vessel disease had significantly
lower EPC counts than those without -- 13 CFU vs. 41.7 CFU," Kunz said.
"Additionally, for every 10 CFU increase in EPC level, a patient's
likelihood for multi-vessel disease declined by 20 percent." 

While the EPC levels did not vary significantly by age, gender or other
risk factors, the researchers found that the levels were lower for
diabetics (19 CFU vs. 36 CFU) and for patients who had suffered a recent
heart attack (23 CFU vs. 34 CFU). 

"These findings demonstrate a strong inverse relationship between
circulating EPCs and coronary artery disease, independent of traditional
disease risk factors," Kunz said. 

The researchers said that it might ultimately be possible to forestall or
even prevent development of atherosclerosis by injecting these cells into
patients or by retraining the patient's own stem cells to differentiate
into progenitor cells capable of arterial repair. 

While the direct clinical use of stem cells as a treatment might be many
years off, the researchers said it is likely that strategies currently
used to reduce the risks for heart disease -- such as lifestyle
modifications and/or different medications -- preserve these rejuvenating
cells for a longer period of time, which delays the onset of
atherosclerosis. 

"On the diagnostic front, it may be possible to take blood samples from a
young person, and depending on measurements of the EPC levels, begin
taking actions early that prevent the depletion of EPCs," Kunz said.
"These cells might also be able to forestall the development of
congestive heart failure in patients who have suffered a heart attack. In
these ways, EPCs can play an important role in both primary and secondary
prevention." 

Other members of the Duke team were Grace Liang, Florim Cuculoski, David
Gregg, M.D., Korkut Vata, Pascal Goldschmidt, M.D., Chumming Dong, M.D.,
Doris Taylor, Ph.D., and Eric Peterson, M.D. 
 

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