Measuring artery repair cells could become new heart disease test

DURHAM, N.C. A more accurate method for measuring blood levels of specialized cells that circulate in the bloodstream and repair damage to the arterial lining has been discovered by Duke University Medical Center cardiologists. These cells, known as endothelial progenitor cells (EPC), are produced in the bone marrow and travel to the site of arterial damage.

The researchers said that tests for EPCs could be used to assess a patient's degree of coronary artery disease or risks for suffering a heart attack, and they could become as routine as the cholesterol and lipid tests cardiologists now commonly use. Patients with lower levels of circulating EPCs would be less able to repair cardiac damage. Thus, they would be those with greater disease and at greater risk for a cardiac event, said the Duke cardiologists

Additionally, the researchers found that the EPC levels correlated with the degree of coronary artery disease. Patients with no coronary artery disease had about 70 percent more EPCs than those who had disease in several coronary vessels.

Recent Duke research has linked the progression of the artery-clogging disease atherosclerosis to the inability of EPCs to continuously repair damage to the arterial lining. Duke researchers have shown that -- while risk factors such as poor diet, smoking, high cholesterol levels and inactivity are important in the development of atherosclerosis --the disease progresses as the body's loses its intrinsic ability to repair and rejuvenate itself.

Current methods for measuring EPCs which can represent as few as one out of 10,000 cells in a given blood sample are subjective and time-consuming, the researchers said. As an indicator of EPC cell levels, the new method uses measurements of the amount of a detoxification enzyme, known as aldehyde dehydrogenase (ALDH), which is produced in high amounts by EPCs.

"Our studies have shown that using ALDH activity to determine the numbers of EPCs in a blood sample might be a better method for identifying and measuring EPC levels in patients with heart disease than currently used methods," said Duke cardiologist Thomas Povsic, M.D. Povsic presented the results of the Duke research March 12, 2006, during the 55th annual scientific sessions of the American College of Cardiology in Atlanta.

"In order for the use of EPC to become practical in human patients, we need an assay that is quick, reliable and accurate," said Povsic. "Since there are so few EPCs circulating, we literally need a method that can find a needle in a haystack. Our tests so far measuring using ALDH activity to measure EPCs represents a novel approach to solving this problem.

"The paradigm of atherosclerosis is changing. In the past we only thought of the risk factors we could measure, such as cholesterol, lipids and some new markers like c-reactive protein," Povsic continued. "We're learning that atherosclerosis is a balancing act between damage and repair, and now we may have a test that gives us insight into the repair portion of the equation."

"If the results of this study are borne out, measuring EPCs could be a better test for defining an individual patient's risk for heart disease," Povsic said. "Theoretically, patients who are found to have low levels of EPCs would be those patients we may want to treat more aggressively."

ALDH is produced in high amounts by stem cells in the bone marrow as part of the process of maintaining the longer lifespans of these cells. Researchers have used ALDH assays to measure the number of stem cells in the bone marrow, so the team has extended this assay to detect levels of EPCs, which are progenitor cells in the blood which may repair one's arteries.

Current methods for measuring EPCs are conducted in the laboratory and are laborious and time-consuming, Povsic said. Researchers first remove all the immune system cells from a blood sample, then culture the remaining cells and then count individual of EPC colonies that grow. The new system permits researchers to gauge the number of EPCs based by identifying those cells with a high amount of ALDH activity.

The Duke researchers based their studies on analysis of blood samples taken from 229 patients who underwent a cardiac catheterization at Duke University Hospital. The researchers found a close relationship between the amount of coronary artery disease and levels of EPCs in the blood as determined using the ALDH test.

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The study was supported by Duke's Department of Medicine, the Duke Clinical Research Institute, Aldagen, Inc., and the Medtronic-Duke Strategic Alliance. Povsic has no financial interest in any funding source.

Other members of the Duke team were Katherine Lambeth, Francince Kelly, Enrikas Vainorious, Michael Sketch, Pascal Goldschmidt and Eric Peterson.


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