November 17, 2000

Vaughan leading team to study genetic links of vascular diseases

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Dr. Mildred Stahlman stands with Dr. Kerry Ross and Dr. Tara Mosley, who attended college with the aid of scholarships provided by Stahlman. (photo by Dana Johnson)

Vaughan leading team to study genetic links of vascular diseases

For more than a decade, Dr. Douglas E. Vaughan, C. Sidney Burwell Professor of Medicine, professor of Medicine and Pharmacology and chief, Division of Cardiovascular Medicine, has explored the role of the body’s clot dissolving system in the development of coronary disease and stroke.

Now, he is leading a collaborative team to explore new genetic factors that may predispose people to arterial and cerebral thrombosis. This work, funded by a $5 million grant from the National Institutes of Health, will support research designed to help unravel the mystery of the genetic causes of vascular diseases.

“We know that there are important, genetically defined factors that increase the risk of stroke and heart attack,” Vaughan said. “This new program focuses on the genes of the plasminogen activator system, which is the clot-dissolving system in humans. We hope to identify genetic factors that influence the activity of this clot-dissolving system.”

Arterial thrombosis is the underlying cause of myocardial infarction, peripheral vascular occlusion and most cases of non-hemorrhagic cerebrovascular stroke, Vaughan said. With the information gathered, the team hopes it will be able to pinpoint the genetic abnormalities in humans that lead to the formation of blood clots in the heart and brain.

“Targeting the key genes and understanding how they interact with each other and the environment to produce arterial thrombosis will have a significant impact on public health in a number of ways,” he said. “This work will eventually aid in identifying individuals at increased risk for developing arterial thrombosis and help us to tailor risk prevention strategies. It may also provide new insights that will be vital for the development of safer and more effective therapies to prevent heart attack and stroke.”

The five-year collaboration is another example of the success of the Meharry-Vanderbilt Alliance, and will also involve scientists from Europe and Africa. The collaboration will involve a team from five academic institutions including Vanderbilt, Meharry, Yale University, the University of Groningen in the Netherlands, and the University of Ghana.

The team is using existing DNA samples collected from American, European and African population studies and intervention trials to test their hypothesis in groups of different ethnic background and with different cardiovascular risks.

Vaughan had previously been involved in work that helped identify that elevated plasma levels of plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen activator (t-PA), and t-PA/PAI-1 complexes are markers for increased risk of myocardial infarction and/or stroke.

“We will identify genetic factors that influence our ability to dissolve clots,” Vaughan said. “We have already found important ethnic differences in circulating PAI-1 levels, and that African Americans have a higher PAI in the plasma – which suggests that there are important genetic determinants.

“We are exploring these populations very carefully. There are also important gender differences in these factors as well. The work we are doing should strengthen efforts over the next decade to identify those individuals most likely to benefit from environmental and lifestyle modifications.”

Other investigators involved in the study include: Dr. Nancy J. Brown, assistant professor of Medicine and Pharmacology; Jason Moore, Ph.D., assistant professor of Molecular Physiology and Biophysics; and Patricia Hebert, Ph.D., who recently left Vanderbilt but will continue the collaboration at Yale University.