Ability of Statins to Improve Heart Failure is Focus of Research
Release Date 2/14/08
Contact
Lois Baker
ljbaker@buffalo.
716-645-5000 ext 1417
BUFFALO, NY. -- Cardiac researchers at the University at Buffalo have
received a four-year, $512,000 grant from the U.S. Department of
Veterans Affairs to investigate how a common cholesterol-
drug increases cardiac-muscle cells and helps to stem the progress of
heart failure.
The research group, headed by John M. Canty, Jr., M.D., UB Albert and
Elizabeth Rekate Professor and chief of the Division of
Cardiovascular Medicine in the School of Medicine and Biomedical
Sciences, demonstrated in earlier research that pravastatin, used
widely to lower blood cholesterol, increases the concentration of
endogenous stem cells from bone marrow that participate in cardiac
repair.
The goal of this new work is to develop pharmacological and cell-
based approaches to treat ischemic cardiomyopathy in patients before
advanced heart failure develops. Heart failure is a condition in
which the heart can not pump enough blood to the body's organs. It is
classified into four stages, from mild, with no symptoms, to severe,
characterized by the inability to carry out any physical activity
without discomfort.
The research is being conducted in UB's Center for Research in
Cardiovascular Medicine, which Canty heads. Gen Suzuki, M.D., Ph.D.,
research assistant professor of medicine who conducted the previous
stem cell studies, is co-investigator. Vijay Iyer, M.D., Ph.D., and
Thomas Ciamato, M.D., Ph.D., both research assistant professors of
medicine, also are involved in the study.
Earlier research conducted elsewhere had shown that HMG-CoA reductase
inhibitors (statins) increase the number of circulating bone-marrow-
derived, or hematopoietic, stem cells in blood, but most of that work
had focused on statins' effects in improving blood flow. Localization
of the statin-induced stem cells in the heart or the ability of
statins to increase cardiac-muscle-
until the UB work.
The UB study employs the cardiovascular research center's unique
swine model of hibernating myocardium, a condition in which cardiac
muscle cells, or myocytes, reduce their contraction yet remain
viable in areas that have received reduced blood flow over an
extended period of time due to narrowed arteries.
In preliminary studies, researchers treated normal pigs and pigs with
hibernating myocardium with pravastatin for four weeks and compared
the results. Results showed that high doses of pravastatin increased
the number of stem cells that localized in hibernating muscle.
In addition, many newly formed myocytes were detected. While
increased stem cells also were seen in normal hearts after
pravastatin, they resulted in myocyte growth and development only in
diseased hearts.
To carry out their new studies, the researchers will develop a swine
model of ischemic heart failure by artificially narrowing two of
three coronary arteries.
They hypothesize that using high doses of statins can prevent the
progression of heart failure in this model by recruiting stem cells
to strengthen the heart muscle, resulting in improved function of the
left ventricle, the primary pumping chamber.
"Statins have been widely employed to reduce coronary events and
improve prognosis in patients with established coronary artery
disease, as well as for primary prevention in patients with high
cholesterol that have other coronary risk factors," said Canty.
"The mechanisms responsible for their beneficial actions have focused
largely on the favorable effects of cholesterol lowering on
atherosclerotic plaques, as well as on the endothelium or inner
lining of the blood vessel wall," Canty said. "Stabilization of
atherosclerotic plaques and improvement in endothelial-
vessel relaxation have been thought to be the major explanations for
their beneficial actions.
"The ability of this class of drugs to induce endogenous repair of
the heart may have been under-appreciated,
statins may have been enhancing endogenous stem cell repair for years
without us realizing it.
"Importantly, it is possible that the beneficial effect on stem cells
is related to an effect of statins independent of cholesterol
lowering. When patients are taken off statins, they might lose these
beneficial effects, as well as the benefits of cholesterol lowering.
Thus, how cholesterol is lowered and with which drug class may be
important in determining all of the beneficial effects of treatment."
Canty, head of the Cardiovascular Disease Group at UB's New York
State Center of Excellence in Bioinformatics and Life Sciences, noted
that when the mechanisms underlying the induction of new cardiac stem
cells are fully understood, there may be other drugs that will
produce results better than statins for treating heart failure.
The University at Buffalo is a premier research-intensive public
university, a flagship institution in the State University of New
York system and its largest and most comprehensive campus. UB's more
than 28,000 students pursue their academic interests through more
than 300 undergraduate, graduate and professional degree programs.
The School of Medicine and Biomedical Sciences, School of Dental
Medicine, School of Nursing, School of Pharmacy and Pharmaceutical
Sciences and School of Public Health and Health Professions are the
five schools that constitute UB's Academic Health Center. Founded in
1846, the University at Buffalo is a member of the Association of
American Universities.
The University at Buffalo is in full compliance with mandates of
state and federal regulatory agencies pertaining to the humane use
and care of research animals.
http://www.buffalo.
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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