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Statins May Simulate Stem Cells for Heart Repair
Nov. 16, 2005 - The drug pravastatin, which is used
widely to decrease high cholesterol, may provide a previously unknown
cardiovascular benefit in addition to lowering lipids. Researchers have
found the statin also increases
the concentration of endogenous stem cells that may participate in
cardiac repair.
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Researchers at the University at Buffalo have found
that pravastatin, the generic name of one of the statins currently
prescribed to lower cholesterol, increased the concentration of
endogenous stem cells that may participate in cardiac repair independent
of any cholesterol-lowering action.
Pravastatin is the generic name of Pravachol, one
of the statin drugs.
The researchers at the University at Buffalo also
found that high doses of pravastatin improved cardiac function and
coronary blood flow in an animal model in which flow had been
artificially restricted, creating a condition known as hibernating
myocardium. In this condition, heart cells reduce their function and
oxygen needs and become dormant in response to insufficient blood flow.
Results of the study were presented today at the
American Heart Association's 2005 Scientific Sessions in Dallas, Texas.
"It is well known that stem cells have the potential to regenerate
organs," said Gen Suzuki, M.D., Ph.D., research assistant professor in
the UB School of Medicine and Biomedical Sciences and first author on
the study.
"In the field of cardiology, adult stem cells
isolated from bone marrow currently are being used to repair damaged
heart tissue," Suzuki said. "Many animal and early clinical studies
using this source of stem cells are ongoing right now."
Earlier reports have shown that HMG-CoA reductase
inhibitors, known as statins, increased the number of circulating
bone-marrow-derived or hematopoietic stem cells in blood, Suzuki said,
but most work has focused on their effects in improving blood flow.
Their localization in the heart or ability to increase
cardiac-muscle-cell numbers has never been studied, he said.
The UB study employs a unique swine model of
hibernating myocardium created by scientists in UB's Center for Research
in Cardiovascular Medicine. Researchers treated normal pigs and pigs
with hibernating myocardium with pravastatin for four weeks, and
compared the results with normal pigs and pigs with hibernating
myocardium that did not receive the statin.
They found that high doses of pravastatin increased
the number of stem cells that localized in both normal and hibernating
hearts. Cardiac function and coronary blood flow improved in the
hibernating hearts, but did not change in normal hearts.
In addition, many newly formed myocytes -- heart
muscle cells that aid in repair of damaged tissue -- were detected.
While increased stem cells were seen after pravastatin in normal hearts
as well, they only resulted in myocyte growth and development in
diseased hearts, results showed.
"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 John
Canty, M.D., Albert & Elizabeth Rekate Chair in Cardiovascular Disease
at UB and senior author on the study.
"The mechanisms responsible for their favorable
effects have largely focused on the blood vessel wall," said Canty,
professor of medicine and physiology at UB and the Buffalo Veterans
Affairs Medical Center. "Stabilization of atherosclerotic plaques and
improvement in endothelial-mediated blood vessel relaxation have been
thought to be the major explanations for their beneficial actions.
"These new findings raise the possibility that
statins can also recruit endogenous repair of cardiac muscle cells in
some disease states. This could lead to a broader application in
treating heart failure arising from cardiac-muscle-cell loss."
About the information:
The research was funded by the American Heart
Association, the National Heart Lung and Blood Institute and the
Department of Veterans Affairs.
The University at Buffalo is a premier
research-intensive public university, the largest and most comprehensive
campus in the State University of New York. The university is in
compliance with mandates of state and federal regulatory agencies
pertaining to the use and care of research animals.
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