Newest cholesterol carriers isolated.

Newest Cholesterol Carriers Isolated

Just when you thought you knew all the players in the cholesterol saga, investigators have isolated and purified two additional particles that may thicken the plot. Normally present in the spaces between cells, these cholesterol-carrying compounds can accumulate into larger deposits that may play a very early role in coronary artery disease -- appearing even before the telltale fatty streaks that often precede hardening of the arteries.

This latest twist in the cholesterol story began in the mid-1980s, when pathologist Howard S. Kruth at the National Heart, Lung, and Blood Institute detected two previously unknown types of cholesterol-rich particles in human and animal arteries narrowed by atherosclerosis. One was bound to fatty acids, essentially making it an oil droplet; the other was a multilayered sphere unbound to fatty acids (unesterified).

Although most research had focused on cholesterol inside cells, these particles appeared only in the spaces between cells. In subsequent work, Kruth and his co-workers observed the unesterified particles accumulating -- even before fatty streaks appeared--in the arteries of rabbits fed high-cholesterol diets. As cholesterol-induced arterial damage progressed, the team found higher concentrations of the unesterified cholesterol particles and smaller but increasing amounts of the oil-droplet type.

Kruth says previous studies missed these particles because most investigators did not look for extracellular cholesterol and because the unesterified particle cannot absorb the dye commonly used to study cholesterol-carrying compounds.

He and his co-workers report in the January AMERICAN JOURNAL OF PATHOLOGY that they have now isolated and purified the two cholesterol-rich particles from human aorta tissue. They have also used electron microscopy and chemical separation techniques to further probe the structure of the compunds, confirming and extending the findings of several research groups that have imaged the particles in arteries.

The team found that the two particle types were similar in size--about 10 times bigger than the familiar high-density and low-density lipoproteins (HDLs and LDLs) that carry cholesterol in the bloodstream. Kruth conjectures that the extracellular particles may serve as storage containers for cholesterol excreted by cells that contain too much of the fatty compound. John Guyton of the Baylor College of Medicine in Dallas, who has performed several electron microscopy studies of the particles, says he is searching for a possible chemical factor linking HDL, LDL and the newly isolated cholesterol-rich compounds.

Kruth told SCIENCE NEWS he and his collaborators recently found that HDL dissolves the unesterified particle in the test tube. In other new experiments, he says, his research group has discovered a link between that particle and LDL: When an enzyme robs LDL of its oily core, the LDL swells like a popped kernel of corn until it resembles the unesterified compound in size and structure.

"What's exciting about this work is that these particles appear before cholesterol accumulates as deposits in cells of the artery wall," Kruth says. "Our studies suggest that we should look for drugs that facilitate the removal of cholesterol that accumulates outside cells."

Deposits of these particles may not always lead to atherosclerosis, cautions Russell Ross, a pathologist at the University of Washington School of Medicine in Seattle. "But this is one possible route," he says.