Statins May Stimulate Stem Cells for Heart Repair

BUFFALO, N.Y. -- The drug pravastatin, which is used widely to decrease high cholesterol, may provide a previously unknown cardiovascular benefit in addition to lowering lipids.

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.

They 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 (Nov. 16, 2005) 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."

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.