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Cholesterol-Lowering Drugs May Boost Blood Vessel Growth

Aug. 29, 2000 -- It's been an ongoing mystery why the wildly popular cholesterol-lowering drugs known as statins also have beneficial effects -- such as reducing heart disease -- in people with normal cholesterol levels. Now, researchers may have an explanation: They found that one of these drugs, called simvastatin, induces the growth of new blood vessels in the injured hind legs of rabbits.

The growth of new blood vessels, known as angiogenesis, can improve function and reduce discomfort in disease-damaged organs and tissues by increasing the flow of oxygen-rich blood.

"For the first time, we've demonstrated in laboratory animals a new activity of statins," lead researcher Kenneth Walsh, PhD, tells WebMD. "We were able to demonstrate very clearly ... that statins promote blood vessel formation in an animal model." Walsh is a professor of medicine at Tufts University School of Medicine and director of the cardiovascular research program at St. Elizabeth's Medical Center in Boston.

While investigating various molecules involved in communication between cells, Walsh's laboratory team was surprised to discover that AKt, a protein found in the cells lining blood vessels that is known to be directly involved in angiogenesis, was activated by simvastatin.

The team decided to test whether simvastatin would in fact induce blood vessel growth in animals with normal cholesterol levels. They injected the drug into the injured hind limbs of rabbits, then used a mapping method in which dye is injected into blood vessels to evaluate vessel growth. "We were able to document that statin treatment of these animals led to enhanced blood flow, presumably as a result of increased vessel growth," says Walsh.

Compared with another group of rabbits that was given saline injections, those that received simvastatin had both increased blood vessel growth and increased numbers of capillaries in their injured limb muscles, he says. Additional testing also showed that the legs of the statin-treated rabbits had increased blood pressure, which also indicates an increase in the number of blood vessels. The study findings were published in the journal Nature Medicine.

According to Michael Simons, MD, director of the Angiogenesis Research Center at Beth Israel Deaconess Medical Center in Boston, the results are valid and the experiments well-designed, but "the authors went a little far in saying that this is an angiogenic [blood vessel forming] agent." He tells WebMD that he suspects that simvastatin is not actually inducing the growth of entirely new vessels, but merely preventing the breakdown of those that naturally grow in response to injury.

Walsh says that it's premature to doubt the results, since additional work is needed before the findings could ever be applied to human patients. Only studies in people will determine whether statins are truly effective at inducing blood-vessel growth, he says. And if they are, it could eliminate the need for any more expensive and controversial gene-therapy research for vascular disease.