Rabbits Reveal Clue to Treating Killer Disease
A team of researchers in San Diego has found what they believe is a method of inhibiting hardening of the arteries in rabbits--a technique they say may point eventually to a new form of therapy for atherosclerosis in humans.
The researchers at the UC San Diego School of Medicine say they have the first clear evidence that it is possible to interfere with atherosclerosis at the cell level in animals by blocking the process by which circulating fat molecules stick to artery walls.
“What it may mean is that we have a new target for preventing atherosclerosis,” said Dr. Daniel Steinberg, a co-author of a paper on the research published in the issue of Proceedings of the National Academy of Sciences coming out today.
Major Cause of Death
Steinberg and Dr. Thomas Carew, the paper’s principal author, emphasized that additional studies must be done to confirm the finding in animals and explore the treatment’s applicability in humans before it could be tried on patients.
Atherosclerosis is characterized by the accumulation of fatty deposits on artery walls. Untreated, the buildup can clog arteries and lead to coronary artery disease, the major cause of death by disease in the United States.
Carew’s team observed that fat protein molecules must be chemically modified before they can form atherosclerotic lesions on artery walls. They hypothesized that the modification involved oxidation, or the attachment of an oxygen molecule to the fat molecule.
To test that hypothesis, they studied 28 Watanabe rabbits, a breed with naturally high blood cholesterol levels. The team fed 11 of the rabbits a drug called probucol, an antioxidant that blocks modification of low-density lipoprotein (LDL), the key fat molecule.
According to the published findings, the treated rabbits ended up with half the number of atherosclerotic lesions found in the untreated rabbits. The researchers concluded that by blocking LDL oxidation, they had reduced the severity of the disease.
Used in Treatment
Probucol is used in the United States and abroad for treatment of excessive cholesterol in the blood. But the researchers said the effect they observed came from its antioxidant properties and appeared unrelated to the mechanism by which it lowers cholesterol.
Nevertheless, to ensure that all the rabbits’ cholesterol levels were comparable, the team fed the other group another cholesterol-lowering drug, lovastatin. The blood cholesterol levels in both groups were the same but the probucol group developed fewer lesions.
If it eventually proves applicable to humans, the researchers said anti-oxidative therapy would likely be used in combination with other therapies to counter atherosclerosis.
“Our hope is that this work will lead to combination therapies that employ cholesterol-lowering drugs, diet and drugs that inhibit LDL metabolism,” Carew said in a statement released by the university.
