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Release: July 10, 2002

Photo: Frank Faraci, Ph.D., UI professor of internal medicine and pharmacology and lead investigator of the program for the past five years.

UI Gets $6.8 Million Grant Renewal For Brain Blood Vessel Studies

University of Iowa investigators have received a major grant renewal for a research program that allows them to study cerebral vascular biology -- how blood vessels function in the brain under normal and diseased conditions. The National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health (NIH), awarded the five-year, nearly $6.8 million grant renewal, which is effective from June 2002 to May 2007.

It is the fourth NIH grant for the UI Cerebral Vascular Biology Program, which was established with NIH support in 1987. The program received five-year grant renewals in 1992 and 1997. A major focus of the now 15-year program is to better understand what happens to blood vessels that supply the brain when risk factors exist for carotid artery disease and stroke, said Frank Faraci, Ph.D., UI professor of internal medicine and pharmacology and lead investigator of the program for the past five years.

"Our basic goals are to learn more about how cerebral blood vessels function normally and then to understand abnormalities in these vessels that cause clotting or contribute to stroke or vasospasm in the brain," Faraci said. "We focus on what goes wrong, that is, what abnormal mechanisms get activated and contribute to vascular disease. We also are trying to better define the protective mechanisms that may work for a while but eventually fail with chronic disease.

"If you can better understand these functions, then you can potentially design drugs or therapies to appropriately affect these mechanisms," he added.

A stroke, or "brain attack," occurs when blood supplied through a carotid artery or other blood vessel to the brain is cut off (ischemic) or when a blood vessel in the brain ruptures, causing blood to leak into the spaces around blood cells (hemorrhagic). The two carotid arteries are located in the neck and are the major source of blood supply to the head.

The UI program includes four major projects, each led by a different investigator within the UI Roy J. and Lucille A. Carver College of Medicine. Collectively, the studies examine how the following conditions affect the structure and function of brain blood vessels: high blood pressure (hypertension), diabetes, inflammation, high cholesterol (hypercholesterolemia), and high homocysteine (hyperhomocysteinemia).

Faraci said the teams rely heavily on the use of two approaches to study and define the changes that occur at the molecular level within the blood vessel wall. These approaches include studies of genetically altered mice and gene transfer methods.

A large number of publications have resulted from the UI program's first 15 years of research. Recently, one project contributed to the identification of homocysteine as a risk factor that has effects like those of high cholesterol. Research within the UI program has demonstrated that the amino acid homocysteine produces carotid and cerebral vascular dysfunction that may contribute to blood clotting by damaging endothelial cells lining the arteries.

"With high levels of homocysteine, cerebral blood vessels become dysfunctional, and the likelihood of stroke goes up," Faraci said.

In addition to Faraci, UI investigators involved in one or more of the four study areas are: Donald Heistad, M.D., UI Foundation Distinguished Professor, and the Zahn Cardiology Professor in internal medicine; Carol Gunnett, Ph.D., associate research scientist in internal medicine; Gary Baumbach, M.D., professor of pathology; Steven Lentz, M.D., Ph.D., associate professor of internal medicine; and Curt Sigmund, Ph.D., professor of internal medicine and physiology and biophysics. Heistad, Baumbach and Lentz also are staff practitioners at the Veterans Affairs Medical Center (VAMC) in Iowa City. In addition, Heistad and Lentz are VAMC researchers.

Faraci noted the importance of the collaborative effort behind the Cerebral Vascular Biology Program.

"I believe that our program is an excellent example of how focused collaboration results in accomplishments that truly are greater than the sum of the parts," he said. "You get much more done working together in a synergistic manner toward a common goal."

According to the American Stroke Association, a division of the American Heart Association, each year nearly 700,000 Americans have a stroke, and nearly 160,000 die from the condition. Stroke is the third leading cause of death in the United Sates and a leading cause of severe and often permanent disabilities. The American Stroke Association can be visited online at www.strokeassociation.org/.

Visit the National Institute of Neurological Disorders and Stroke at www.ninds.nih.gov/.