Plaque Vaccine Shows Promise

Mouse study holds promise for treating human artery disease

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By
HealthDay Reporter

MONDAY, March 18, 2002 (HealthDayNews) -- Scientists in the United States and Sweden are reporting early success with a mouse version of a vaccine that prevents dangerous plaques from forming in the arteries.

Plaque buildup, or atherosclerosis, narrows the arteries and leads to blood clots that can set off heart attacks or strokes. Breakaway deposits from the lesions can also cause these maladies, especially strokes. In theory, preventing plaque formation before it gets a foothold in the vessel wall would avoid those troubles down the road.

"It would be wonderful if you could eliminate all plaque," says Dr. James E. Muller, director of clinical research in cardiology at Massachusetts General Hospital in Boston. "This is an exciting, novel approach."

Dr. P.K. Shah, of Cedars-Sinai Medical Center in Los Angeles, and Dr. Jan Nilsson, of Lund University in Malmö, Sweden, led the latest experiments, which have so far only been conducted in mice. The work was presented today at a meeting in Atlanta of the American College of Cardiology.

Cholesterol molecules called low-density lipoprotein (LDL) that lodge in vessel lining and are oxidized cause artery plaques. Once oxidized, the immune system assaults the LDL, producing inflammation that makes the area an unstable mass vulnerable to breakaway bits.

"What one really wants to aim at is stabilizing plaques rather than making them disappear completely, which is impossible," Nilsson says. "If you can get that to cool down, that's eventually what we want to obtain" with a vaccine.

About a decade ago, Nilsson says, doctors noticed patients with atherosclerosis had blood proteins, or antibodies, signaling an immune reaction to LDL. They at first thought plaque formation was an autoimmune reaction, similar to arthritis.

However, tests in animals showed the antibodies appear in response to, not as the trigger for, plaques. What's more, Nilsson says, researchers found they could prevent plaques from forming in mice by injecting the animals with oxidized LDL. In other words, they created a crude vaccine.

Since LDL is a large, complex molecule, Shah, Nilsson and their colleagues sought to simplify their approach. The scientists broke LDL into smaller structures, and tested these in human blood to see what proteins reacted to the chunks.

The researchers then tested some of these proteins, known as peptides, in mice that were genetically engineered to have abnormally high cholesterol levels and be vulnerable to heavy plaque formation.

In the California research, the animals received injections of two peptides when they were six weeks old, followed by a booster shot at nine weeks of age.

One of the peptides had no effect on plaque formation, compared with a dummy shot. However, mice that received the second molecule, P2, had only about a third the plaque area of the other two groups. They had less inflammation at the site of the lesions, and the plaques themselves contained more collagen than those in the other animals -- suggesting they were more stable and less likely to shear off the vessel wall.

In the Swedish study, Nilsson's group tested a mixture of peptides, on the theory that the lot of them would be more protective than a single protein.

The results were similar: animals that received the vaccine had about 60 percent to 70 percent less plaque area than untreated mice, and the lesions they did have were firmer with collagen.

Nilsson said the studies together suggest not only that a plaque vaccine is possible, but that a single protein might be sufficient. He and his colleagues hope to test a version of the injection in humans within about two years.

What To Do

In the meantime, there are steps you can take to prevent atherosclerosis, including reducing your LDL cholesterol. Quit smoking, cut down on animal fat in your diet and exercise regularly.

If your cholesterol count doesn't improve with lifestyle changes, drugs called statins are effective at controlling blood fat. Seek your doctor's advice.

For more on atherosclerosis, try the American Heart Association or the Office on Women's Health.

SOURCES: Jan Nilsson, M.D., Ph.D., professor, medicine, Lund University, Malmö, Sweden; James E. Muller, M.D., director, clinical research in cardiology, Massachusetts General Hospital, Boston; March 18, 2002, American College of Cardiology meeting abstract

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