CONTACT: BECKY SOGLIN
Iowa City IA 52242
(319) 335-6660; fax (319) 384-4638
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
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,"
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
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/.