Chronic stress can induce rapid blocking of
arteries after a balloon angioplasty procedure
November 17, 2005
Chronic stress accelerates atherosclerosis following angioplasty procedure,
according to research performed in animal studies at Georgetown University
Medical Center. Blocked coronary arteries after angioplasty affect 41 percent of
patients who undergo the procedure and can lead to death.
But the Georgetown scientists also demonstrated that this stress-induced
atherosclerosis could be prevented by blocking a certain neuropeptide in blood
vessels. They say the results, published in the October issue of the American
Heart Association journal Arteriosclerosis, Thrombosis and Vascular Biology, may
someday lead to targeted therapy for individuals at risk for the condition.
The study is the newest in a series of animal studies that shows how chronic
stress can be a high risk factor for accelerated atherosclerosis, a heart
condition where plaque-like substances build up in the inner lining of an artery
and can lead to heart attack or stroke. The study showed that the effects of
stress were more rapid than the effects of a fat-rich diet in causing
atherosclerosis.
"Stress is a newly emerging risk factor for cardiovascular disease but
until now, we didn't know the exact mechanism involved," said Zofia
Zukowska, MD, PhD, Professor of Physiology and Biophysics at Georgetown
University Medical Center. "This research provides the first
well-documented, experimental evidence in animals that stress can actually
induce triggers that lead to vessel blockage and atherosclerosis."
In the study, researchers performed an angioplasty procedure on two groups of
rats, and then induced stress in the experimental group. Follow-up tests carried
out after just two weeks of daily stress showed that this stress significantly
increased blood pressure and doubled circulating levels of neuropeptide Y (NPY)
compared to rats that did not undergo stress. NPY is a neurotransmitter present
in the nerves surrounding blood vessels which become activated by stress.
Stress-activated nerves then release NPY onto the cells within the vessel wall,
where it exerts several potent actions.
Previously, researchers knew that NPY could cause acute narrowing of the vessel
by contraction of its muscular wall. However, this study showed that it has even
more profound effects when it its levels are elevated chronically. In stressed
rats which underwent angioplasty, NPY stimulated growth of abnormal smooth
muscle in the blood vessels and caused them to become blocked with lesions
containing microphages, thrombus and lipid deposits. These lesions resembled
plaques which develop in humans in a process of atherosclerosis and are the
cause of vessel blocking after angioplasty. This process has never before been
reproduced in normal laboratory animals, unless they were genetically
manipulated or were fed a fat-rich diet.
Researchers also found that it was possible to reverse this process by giving
rats a compound that prevented cells from reading the increased levels of NPY.
This compound, called the Y1 receptor antagonist, completely prevented the NPY-induced
changes, allowing rats to undergo stress without increasing risk for
atherosclerosis.
"This research has great potential for clinical applications in the
future," said Zukowska. "Although this needs more study, if this same
phenomenon occurs in humans, it is possible that Y1 antagonist could be used as
a therapy for at-risk individuals."
Zukowska noted that if validated in humans, the research could be particularly
applicable to men, whose bodies release more NPY during stress and who are
generally more susceptible to heart attacks than pre-menopausal women. The
findings also may prove helpful for individuals with mutations in the NPY gene,
which occurs in some ethnic populations in as high as 9 percent of people, and
which causes nerves to release the neurotransmitter in elevated levels.
Other co-authors on the paper include Lijun Li, PhD, and Ken Abe, MS, from
Georgetown University and Anne-Catherine Jonsson-Rylander, PhD of AstraZeneca,
Sweden, the company which provided Y1 receptor antagonist.
About BGRO
Georgetown's Biomedical Graduate Research Organization (BGRO) was created to
foster cutting-edge, interdisciplinary collaboration and to enhance the
university's research capacity, especially in the areas of child and human
health and development, the neurosciences, cardiovascular-kidney health, and in
shared work with researchers and clinicians from Georgetown's Lombardi
Comprehensive Cancer Center. BGRO is also focused on educational and academic
excellence in the biomedical sciences in order to train the next generation of
scientific researchers in the United States and around the world.
Georgetown University Medical Center is an internationally recognized academic
medical center with a three-part mission of research, teaching and patient care
(through our partnership with MedStar Health). Our mission is carried out with a
strong emphasis on public service and a dedication to the Catholic, Jesuit
principle of cura personalis--or "care of the whole person." The
Medical Center includes the School of Medicine and the School of Nursing and
Health Studies, both nationally ranked, and the world-renowned Lombardi
Comprehensive Cancer Center.
Liz McDonald
eem6@georgetown.edu
Georgetown University Medical Center
http://gumc.georgetown.edu
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