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New predictor of heart disease risk found

(SACRAMENTO, Calif.) -- Cardiovascular research is increasingly showing that a new predictor of heart disease risk, c-reactive protein, is just as important as monitoring cholesterol levels to prevent and treat heart disease and other ills, including stroke, sudden death and peripheral vascular disease. Now, UC Davis physicians have discovered that this protein is not just a marker for heart disease, but that it actually damages the blood vessel wall by blocking a critical "protector" protein and by promoting plaque formation.

The finding, published in the September 17 issue of the journal Circulation (available on the Web at http://www.circulationaha.org ), describes a new molecular pathway that stimulates plaque formation. The work is important because it provides a new target for drug development efforts, explains why cholesterol screening is not enough to accurately assess heart disease risk, and underscores the need to use c-reactive protein screening to more accurately assess at-risk populations.

In their series of experiments, UC Davis researchers found that c-reactive protein inhibits the activity of a very critical "protector" enzyme in the blood vessel wall. This protector enzyme, called eNOS, or endothelial nitric oxide synthase, produces nitric oxide, which works to keep blood vessels healthy and heart disease at bay by preventing plaques from adhering to blood vessel walls, keeping coronary arteries dilated and inhibiting constriction of smooth muscle cells.

At the molecular level, c-reactive protein decreases the stability of eNOS messenger RNA and prevents the activation of its second-messenger molecule, cyclic GMP. These events prevent eNOS from producing its protective biological effects. C-reactive protein also promotes white-blood-cell binding to blood vessel walls and stimulates the release of other adhesion molecules, including intercellular adhesion molecule 1, or 1CAM-1, and vascular cell adhesion molecule, or VCAM
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Contact: Carole Gan
cfgan@ucdvis.edu
916-734-9040
University of California, Davis - Health System
26-Aug-2002


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