A Deadly SOS From Wounded Arteries

Like a captain on a sinking ship shooting a flare to call for help, arteries in distress attract immune cells. But instead of rescuing arteries, the immune cells appear to accelerate their decline. The findings, reported in today's issue of the Journal of Clinical Investigation, suggest that putting a damper on part of this distress call may be a new way to treat heart disease.

Everyone knows that "bad" cholesterol tends to build up in arteries and often leads to atherosclerosis. But for a host of other risk factors--such as cigarette smoke and certain bacterial infections--the disease-causing mechanism is unclear. One thing these risk factors have in common, however, is that they trigger an inflammatory and repair response, says Robert Terkeltaub of the Veteran's Administration Hospital in San Diego. It was known that a precursor of macrophages--roving cells deployed by the immune system to consume bacteria and dead cells--speeds up fat deposition in scarred arteries.

Terkeltaub enlisted colleagues at The Scripps Research Institute in La Jolla, California, and the University of California, San Diego, to try to pin down how these precursors, called monocytes, might be attracted to the lesions. Working on mice, Linda Curtiss of Scripps transplanted bone marrow that would churn out white blood cells either with or without the mouse version of CXCR-2, a receptor for chemokines--the distress call put out by wounded cells at the lesion. The team fed both groups of mice an artery-hardening diet: the equivalent of a hamburger a day, Terkeltaub says, "and a milk shake on top of that." After 4 months, the mice with the receptor had arterial lesions 2.5 times the size of lesions in mice without the receptor; the CXCR-2 mice also had significantly higher macrophage counts.

The finding shows that altering the immune response can change the course of atherosclerosis, says Alan Tall of Columbia University. The implication, he says, is that compounds that block chemokine receptors might someday be used in people to protect wounded arteries.

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