Antibody Softens Hard Arteries

Like a one-two punch, a fatty diet and the body's own immune system conspire to bring on heart disease. Fat and cholesterol clog arteries and block blood flow, starving the heart of oxygen. In the meantime, this clogging produces plaques that damage the artery wall, attracting immune cells that worsen inflammation. Now researchers appear to have found a way to soften these blows: According to a report in tomorrow's issue of Nature, injections of an antibody dramatically reduced both lesions and cholesterol deposits in mice.

Mice don't normally get hardening of the arteries, so a team led by François Mach and Uwe Schonbeck at Boston's Brigham and Women's Hospital turned to an altered mouse strain unable to break down cholesterol. They fed 10 mice a high-cholesterol diet for nearly 3 months, during which the animals developed arterial inflammation similar to that of humans. With soaring lipid levels and steady plaque buildup, the mice faced a bleak prognosis.

The team then targeted the suspected culprits behind atherosclerotic inflammation--an immune cell called CD40 and its molecular sidekick, CD40 ligand (CD40L), which binds to CD40. The researchers reasoned that, by injecting into the bloodstream an antibody to CD40L, they could prevent CD40 from binding to CD40L and quell the inflammation on the plaque-induced lesions. Indeed, mice given twice-weekly injections of the CD40L antibody for 12 weeks had lesions that became 59% smaller, and contained 79% less cholesterol, than lesions in controls. The finding "points the way" toward new treatment strategies against atherosclerosis, says team member Peter Libby, chief of cardiology at Brigham and Women's.

Others experts echo that cautious enthusiasm. "This is the first step toward a very productive area of research," says Momtaz Wassef, who heads the atherosclerosis research group at the National Heart, Lung, and Blood Institute. Human trials might be years away, but Wassef hopes the antibody could prove out as a powerful weapon against heart attacks and strokes.