Lipoprotein findings may solve one riddle ... and pose another.

Lipoprotein findings may solve one riddle . . . and pose another

A surprising similarity in structure between two blood proteins could help explain how some people develop atherosclerosis, or hardening of the arteries, scientists announced this week. But in giving some answers, the new findings raise other questions.

Scientists from the University of Chicago and Genentech, Inc., of South San Francisco report in the Nov. 12 NATURE that they have determined the sequence of amino acids found in applipoprotein(a), a subunit of lipoprotein(a). Found in the blood, the latter has been tied to the development of atherosclerosis --but the exact mechanism is unclear. Another subunit of lipoprotein(a), called apolipoprotein B-100, already has been fingered as a culprit in atherosclerosis (SN: 2/7/87, p.90).

This week's report contains the first complete sequence of apolipoprotein(a) and offers some insight into the atherosclerosis dilemma. Coauthor John W. McLean of Genentech told SCIENCE NEWS that a report from the group earlier this year had hinted that apolipoprotein(a) might be structurally related to the blood protein plasminogen. Subsequent work has confirmed that similarity, with possible medical consequences, he says.

Plasminogen--the precursor of a blood enzyme that dissolves clots--contains unusual amino acid sequences called kringles, which resemble a Danish cake by that name. Apolipoprotein(a), say the Genentech/Chicago researchers, inexplicably has kringles as well. McLean, who calls the implications of these findings "tantalizing,' says structural similarities between the two could mean that apolipoprotein(a) somehow affects plasminogen's role in clot dissolution.

In an accompanying commentary, Nobel laureates Michael S. Brown and Joseph L. Goldstein, from the University of Texas Southwestern Medical Center in Dallas, agree that these "astounding' results could "provide the long-sought link between lipoproteins and the clotting system.' Some scientists believe that mini-clots on blood vessel walls promote atherosclerosis.

On the basis of their new data, the researchers are planning studies to investigate the possible physiological functions of apolipoprotein(a) and how the protein interacts with known receptors on blood vessel walls. Of interest, says McLean, is an understanding of why different sizes of apolipoprotein(a) are found in different concentrations among individuals. He adds that the protein's structural similarity to plasminogen also could cast doubts on data from already completed studies that measure one or the other.

Beyond the immediate questions about apolipoprotein(a)'s influence in atherosclerosis is its apparently odd place in evolution. It has 37 repeat copies of one kringle section placed end to end, making the protein larger than what would seem necessary. And thus far, the protein seems useless. The gene coding for apolipoprotein(a) has not been found in species lower than primates, and may have first appeared about 40 million years ago, say the authors. "Why is nature carrying along this huge burden of a protein with no known function?' asks McLean. He speculates that there may be "something in man's history that makes [the protein] important for survival.'

The current study does not suggest any potential therapy to prevent atherosclerosis, says McLean. But if there is a correlation between susceptibility to atherosclerosis and apolipoprotein(a) levels, he thinks an assay for the protein could help screen for patients who should adopt exercise routines and watch their nutrition.