Lipoprotein link to heart disease revealed.

High concentrations of the cholesterol carrier lipoprotein(a) in the blood are a known risk factor for heart disease. Indeed, cardiologists estimate that Lp(a) a close cousin1 of low-density lipoprotein, itself a heart threat - may be responsible for up to 25 percent of heart attacks that strike relatively early in life. The trouble is, scientists don't understand the mechanism underlying this molecule's role in the drama of heart disease.

Now, an international scientific team suggests that elevated concentrations of Lp(a) in the bloodstream may cause smooth muscle cells within the artery wall to proliferate. As a cholesterol carrier, Lp(a) also deposits cholesterol and other fatty debris on the vessel's inner wall. The thickening of the blood vessel that results is a hallmark of atherosclerosis.

Biochemist David J. Grainger of the University of Cambridge in England and molecular biologist Richard M. Lawn at the Stanford University School of Medicine grew smooth muscle cells taken from healthy human arteries in laboratory dishes. When the team exposed those cultured cells to Lp(a), the cells began to divide more rapidly than usual. The researchers report their findings in the June 11 SCIENCE.

The new study suggests that Lp(a) interferes with a natural growth-restraining system that operates in human arteries. The group showed that Lp(a) inhibited the activation o! an antiproliferative substance called transforming growth factor-[beta]. Without enough of this activated factor, smooth muscle cells continue their division unchecked, an insidious process that could lead to clogged arteries, Lawn says.

People with high concentrations of Lp(a) in their blood may suffer the double whammy of.too much arterial muscle cell proliferation plus large deposits of cholesterol inside their artery walls. Such a mechanism may explain the elevated risk of heart attack for such people, Lawn adds.

However, both Lawn and Grainger warn that their study only looked at this cholesterol carrier's impact on smooth muscle cells grown in laboratory dishes. The team has yet to determine whether such proliferation takes place in humans.

If it does, cardiologists may one day be able to stave off atherosclerosis in people who produce too much Lp(a), says Grainger. One approach would be to use drugs that block the excess proliferation of smooth arterial muscle cells, he speculates.