Immune cell triggers attack on plaque.

The sudden, often fatal rupture of plaque clogging an artery involves a host of possible villains, including the scavenging immune cells called macrophages. Now, a Finnish team presents evidence that another immune cell, the mast cell, may also take part in this deadly assault.

Atherosclerosis results from the buildup of cholesterol, fatty debris, and other substances on the interior wall of an artery. Normally, a tough protein cap covers this goo and keeps pieces of the plaque from breaking off into the bloodstream. But a fissure in that protective cap may lead to the formation of a clot (thrombus), which can block blood flow to the heart and cause a heart attack.

Petri T. Kovanen of the Wihuri Research Institute in Helsinki and his colleagues studied sections of human coronary arteries removed during 32 autopsies of men and women age 13 to 67. All 32 had some sections of the interior artery wall that appeared healthy and free of fatty buildup. However, 25 of the 32 showed regions with fatty streaks, the beginnings of atherosclerosis, and 19 of the 32 had areas with hardened plaque.

The researchers discovered mast cells in 50 percent of the normal vessel sections, in 84 percent of the fatty streaks, and in 95 percent of the so-called shoulder, a rupture-prone area of the plaque (see illustration).

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The Finnish team proposes that mast cells help crack a coronary plaque by releasing enzymes that help dissolve collagen and other components of the plaque's protein cap.

The group also showed that mast cells in the shoulder regions of plaque are much more likely to be activated than mast cells elsewhere in the artery. Once revved up, these cells spit out a cocktail of cap-melting enzymes and the chemical histamine as well.

Kovanen believes that histamine makes matters worse by causing the coronary artery to contract. If a clot forms when the plaque splits, the histamine-narrowed vessel may become completely blocked, thus leading to a massive heart attack.

The Finnish team reports its findings in the October CIRCULATION.

Mast cells, which are present in the airway and nasal passages, play a key role in hay fever and asthma attacks. However, the researchers say there's no evidence that people with asthma or allergies have an increased risk of heart attack.

What causes mast cells to release their risky products? Smoking may. Kovanen points out that smoking increases IgE, an antibody that helps stimulate mast cells. However, elucidating the basic biology of these cells will require much more research, he says. For example, no one knows how mast cells function in healthy artery walls.

If future research confirms the role of the revved-up mast cell, researchers might attempt a preventive strike with drugs that quiet these cells, comments L. Maximilian Buja, a plaque researcher at the University of Texas Medical School at Houston.