CONTACT: BECKY SOGLIN
Iowa City IA 52242
(319) 335-6660; fax (319) 384-4638
Release: June 28, 2002
NOTE TO EDITORS: The following news release describes a study led
by investigators at the University of California Davis School of Medicine
and Medical Center. William Nauseef, M.D., University of Iowa professor of
internal medicine, was part of the research team. He is available for comment
most of the day Friday, June 28 at (319) 356-1739. For a copy of the UC Davis
release, contact email@example.com or visit http://news.ucdmc.ucdavis.edu/news_release.html.
UI researcher contributes to study linking a specific protein to atherosclerosis
A protein that normally plays a pivotal role in combating bacterial infections
can also contribute to inflammatory disease in blood vessels by altering the
availability of nitric oxide, according to a study published by University
of California at Davis investigators and others, including a University of
The findings on the protein myeloperoxidase (MPO) appear in the June 28
issue of Science. The paper's lead author was Jason Eiserich, Ph.D., assistant
professor of internal medicine and human physiology at the UC Davis School
of Medicine and Medical Center. The results have implications for understanding
and treating atherosclerosis -- the build-up of fats, cholesterol, cellular
debris, calcium and other substances that damage the inner lining of arteries
and result in significant disease and death. The research team included William
Nauseef, M.D., UI professor of internal medicine and a faculty member of the
UI Inflammation Program.
Nauseef heads a long-standing project that studies the structure and function
of MPO, including the functional consequences of different genetic causes
of inherited human MPO deficiency. In previous work his lab identified several
specific mutations in the MPO gene that result in the absence of normally
functioning MPO in humans.
"We developed a system to characterize the functional effects of different
genotypes of MPO deficiency," said Nauseef, who also is a staff physician
and researcher with the Veterans Affairs Medical Center in Iowa City. "We
created cell lines that express normal MPO and lines that mimic the patients'
defects by expressing the mutant, nonfunctional form of MPO. Jason Eiserich
and his team used both of these cells as a source for their tests, and they
were able to demonstrate that the observed changes in blood vessel reactivity
were due to the presence of active MPO."
MPO is normally found in the circulating white blood cells that respond
to acute infection by forming pus. MPO catalyzes the generation of hypochlorous
acid, or bleach, and is essential in efficiently wiping out bacteria. However,
the protein also can participate in inflammatory events that are independent
of infection, such as the acute inflammatory responses seen in gout, rheumatoid
arthritis, many allergic reactions, and stress-related inflammation.
"From the point of view of the host, it's good when MPO kills bacteria
and contributes to resolving an infection, but it's bad when, for example,
it's participating in an acute arthritic attack in a joint such as the knee,"
Blood vessels react to different chemical influences, including nitric oxide,
which is also known as the "vascular relaxing factor." As such,
this molecule helps regulate blood pressure, inhibits blood clotting and prevents
narrowing of the arteries.
Normally, MPO combines with hydrogen peroxide in the presence of chloride
to kill bacteria. However, the investigators found that MPO combines with
hydrogen peroxide and other molecules to form free radicals that then react
with nitric oxide. This chemical reaction thereby reduces the amount of nitric
oxide available to mediate vessel relaxation, thus changing the body's ability
to regulate blood vessel reactivity.
Nauseef said he hopes to continue studying the structural and genetic factors
underlying normal MPO activity.
"Since none of the cells normally present in a fatty plaque normally
possess MPO, the identification of MPO in blood vessels has never been fully
explained," he said. "We believe that certain cells within plaque
acquire the capacity to express the MPO gene because of special proteins such
as cytokines produced within the plaque environment."
If that is true, Nauseef added, then determining the factors that regulate
MPO gene expression might make it possible to interrupt the cycle, as a therapeutic
"There's long been a suspicion that MPO has a role in atherosclerosis,"
Nauseef said. "This finding advances that notion one step further. The
study emphasizes that atherosclerosis is a complex, multifactorial inflammatory
disease and reflects biology far more involved than simply excess fat consumption."
The Department of Veterans Affairs funded Nauseef's research on MPO and
MPO deficiency for this study, and the work was accomplished at the Iowa City
VA Medical Center. The VA has funded Nauseef's MPO research since 1984.
University of Iowa Health Care describes the partnership between
the UI Roy J. and Lucille A. Carver College of Medicine and UI Hospitals and
Clinics and the patient care, medical education and research programs and
services they provide. Visit UI Health Care online at www.uihealthcare.com.