The clogging of an artery.

OAA0009

HDL is good. LDL is bad. Just when people are beginning to remember these basics, scientists re adding new wrinkles.

One of the most exciting ones suggests that it's not just ordinary LDL, but oxidized LDL, that stops up arteries, setting the stage for heart attacks. And much of the credit for this discovery goes to Daniel Steinberg of the University of California at San Diego.

Steinberg and others have spent years trying to figure out precisely how arteries get clogged, and, more to the point, how cholesterol first enters them.

Steinberg's oxidized-LDL theory is "the most promising hypothesis," says Henry McGill of the University of Texas Health Science Center at San Antonio. "No other current idea competes with it."

The Start of a Streak. The first sign that cholesterol has infiltrated an artery's wall is a streak of fat and cholesterol in the wall's lining. Alone, the fatty streak is harmless, but without it, heart disease would have no place to begin.

Understanding the streak doesn't entirely explain heart disease. We still have to figure out what turns the benign streak into a fibrous, bulging "plaque" that can cut off the flow blood, Nevertheless, understanding the streak is critical.

"There is a widespread consensus that the more fatty streaks you have, and the thicker they get, the more likely they are to go on to fibrous plaques," says McGill.

Don't Call a Plumber. Most people think that cholesterol clogs an artery the same way too much sludge clogs a drainpipe. Wrong. "The first thing to understand is that the cholesterol isn't plastered inside the artery," explains Steinberg. "It's inside the cells of the artery wall. "

But which cells? "Most of the cholesterol in a fatty streak lesion is not in the muscle [of the artery wall], but in cells that come from circulating monocytes," says Steinberg. Monocytes, which are white blood cells, are key actors in the body's immune system, he explains. "Their major role is to protect against bacteria or foreign materials." in heart disease, though, monocytes are not such good guys.

Monocytes on Patrol. "Ordinarily," says Steinberg, "monocytes patrol the bloodstream. But they don't normally stick to the arteries. They just swing by."

When animals are switched from a lowfat diet to a fatty, cholesterol-laden one, though, the monocytes start sticking to the artery linings. That's when trouble begins.

The monocytes crawl through the endothelial cells that line the artery, and take up residence in the wall. There, scientists call them macrophages-immune cells that neutralize their enemies by engulfing them. But for several years, researchers were faced with a paradox. They assumed that arteries became clogged by bloated macrophages that had stuffed themselves with LDL.

Yet when they mixed macrophages and LDL in a test tube, says Steinberg, we couldn't force the macrophages to take up the LDL very quickly. " Oxygen Strikes Again. The breakthrough came when Steinberg's research team mixed the LDL with endothelial cells from the artery wall and then offered the LDL to the macrophages. "The macrophages took up the LDL three to ten times faster," he says.

Why? "The endothelial cells were oxidizing the LDL. It took us a year to figure it out."

One clue, he says, was that "if we added vitamin E, BHT [a food additive], or other antioxidants, they protected the LDL from being taken up." And that's good because LDL that isn't engulfed by macrophages cannot clog your arteries.

Hennekens' study on beta-carotene I see page 81 isn't the only reason to think that oxidized LDL invades arteries. Among other evidence: Probucol, a powerful antioxidant drug, slows artery clogging in rabbits that are genetically prone to heart disease. Turncoats. Why should monocytes turn into bad guys when they burrow into the artery wall and become macrophages?

"Oxidized LDL is damaging to tissues," Steinberg explains. So by scooping up oxidized LDL, the macrophages may be trying to defend the body.

But, he speculates, "the macrophages are only capable of handling a low level of oxidized LDL. If your cholesterol level is too high and you live long enough, the system gets overwhelmed."

So far, Steinberg doesn't recommend taking antioxidants. But he does point out: "If we feed animals diets that are rich in monounsaturated fats, their LDL is more resistant to oxidation than when they're fed polyunsaturated fats." Chalk one up for olive and canola oils.

And regardless of how the oxidized-LDL story turns out, Steinberg won't change his advice to eat less saturated fat and cholesterol. "In most people, we can prevent heart disease by keeping blood cholesterol levels down. We know that."

Source.- J Am. Med. Assoc. 264: 3047, 1990.