Simple test predicts ability to grow new blood vessels: Breakthrough in battle against heart disease, diabetes, cancer

August 02, 1999

HAIFA, Israel, and NEW YORK, N.Y., July 30, 1999 -- Some 14 million people suffer from coronary artery disease in the United States, leading to an oxygen-starved heart, angina and risk of heart attack. The human body is able to grow new blood vessels that compensate for the blocked vessels that cause heart attacks. These new vessels may also feed cancerous tumors and cause blindness in diabetes patients. A study at the Technion-Israel Institute of Technology, published in the August 3 Circulation, describes a simple blood test that can predict a person1s ability to grow such vessels. Armed with this knowledge, doctors can better decide on appropriate treatment.

"There are important implications to our findings in terms of treating heart disease, the leading cause of death in developed countries, as well as on cancer and diabetes," said Dr. Andrew Levy of the Faculty of Medicine at the Technion, who led the study. "Coronary patients whose tests show little potential to generate new vessels could be treated with drugs to increase this potential or treated more aggressively with surgery. Cancer and diabetes patients, on the other hand, whose tests show a high potential, would require more aggressive treatment than patients who show a low potential for new vessel growth." He added that while the implications on heart disease are clear, his team is still studying the implications on cancer and diabetes.

The blood test is being readied for commercial use.

Dr. Levy was one of three researchers who in 1989 identified vascular endothelial growth factor (VEGF), the protein that triggers blood vessel growth in a process called angiogenesis.

"The Technion study represents a seminal observation," said Dr. Jeff Isner, professor of medicine at Tufts University and chief of vascular medicine and cardiovascular research at St. Elizabeth Medical Center in Boston. "It not only confirms our own studies on VEGF gene therapy as a 'replacement therapy' but further establishes a novel bioassay to study large numbers of patients."

"This study is important because it shows there are critical differences in cellular behavior between patients with coronary disease," said Dr. William Li, president and medical director of the Angiogenesis Foundation. "By studying these differences, it may be possible to develop a simple blood test to determine a patient's 'angiogenic capacity.'"

Dr. Harry Shamoon, professor of medicine and director of the General Clinical Research Center at Albert Einstein College of Medicine, said Dr. Levy's work may make it easier to identify people at higher or lower risk for diabetic complications and to design therapy geared to individuals.

To test individuals' ability to grow new vessels -- called coronary artery collaterals -- the Technion researchers developed a test for measuring VEGF in the blood. They took blood samples from 51 patients with coronary heart disease. These patients were divided into three groups based on an X-ray of their coronary arteries: those who formed a large amount of collaterals, those who formed intermediate amounts and those who formed no collaterals. From the patients' blood, the researchers isolated the monocytes, a white blood cell, and divided them into two groups, treating one with 1% oxygen -- the amount available to patients suffering from low oxygen supply -- and the other group with 21% oxygen -- the normal amount available to healthy individuals. Then they measured the RNA in the cells, the genetic component responsible for enhancing VEGF and collateral growth. They found that the cells of people who grew more collaterals produced significantly more VEGF in response to the low oxygen supply than those who didn't grow them.

Interestingly, the people who did and did not grow collaterals were roughly equal in number. This means that about 50 percent of coronary disease patients can compensate for clogged vessels by developing new ones. These patients should have fewer heart attacks or may escape them altogether, Dr. Levy explained.

On the other hand, people who grow collaterals may more readily succumb to cancer and the ravages of diabetes. The oxygen that cancerous tumors need to grow is provided by these same collaterals. And as diabetes patients1 retinas become oxygen starved, growth of collaterals leads to retinopathy and blindness.

The Technion team is now completing a study on the connection between the ability to grow collaterals and the development of retinopathy in diabetic patients. The team is also investigating whether genetics or environmental factors are behind individual variances in collateral formation. Dr. Levy believes a genetic component is probably responsible. His soon-to-be-published studies on divided cells (fibroblasts) from the human foreskin of different donors found the cells differed markedly in their production of VEGF.

Dr. Levy said the blood test developed by his team is being prepared for commercial use. Cancer and diabetes patients who grow large amounts of collaterals could be treated more aggressively.

The research team is also examining simple ways to deliver VEGF or to reduce VEGF production. Currently, VEGF is administered by injection or catheter into the heart. Dr. Levy's team would like to find a simple delivery method that involves an oral pill.

"The body has the ability to heal itself. Our goal is to help it do that more easily," he said.
NOTE TO EDITORS: Illustration will be available on our website at

The Technion-Israel Institute of Technology is the country's premier scientific and technological center for applied research and education. It commands a worldwide reputation for its pioneering work in communications, electronics, computer science, biotechnology, water-resource management, materials engineering, aerospace and medicine, among others. The majority of Israel's engineers are Technion graduates, as are most of the founders and managers of its high-tech industries. The Technion's 13,000 students and 700 faculty study and work in its 19 faculties and 30 research centers and institutes in Haifa.

The American Technion Society (ATS) supports the Technion. Based in New York City, it is the leading American organization supporting higher education in Israel. The ATS has raised $726 million since its inception in 1940, half of that during the last seven years. Technion societies are located in 24 countries around the world.

American Society for Technion - Israel Institute of Technology

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