CRP is conventionally regarded as a first-line defense of the immune system against invading pathogens and confers protection to humans by removing pathogens. Recently, CRP has been reported as a useful marker for predicting future atherosclerotic cardiovascular events, but the basis for this correlation remains unclear.

Although scientists still do not understand all the steps in the development of atherosclerosis, it is known that oxidized LDL in the artery wall are taken up (engulfed) by macrophages, scavenger cells that have been drawn to the site by oxidized LDL. When they become engorged with the oxidized LDL, the macrophages become "foam cells," the hallmark of atherosclerotic plaques. It is possible that CRP may bind to oxidized LDL and further enhance the uptake into cells.

The paper's senior author, Joseph Witztum, M.D., professor of medicine, added that cholesterol is still a key player in coronary heart disease. He said that CRP may be working in its "correct role" as part of the immune response to the toxic oxidized LDL and may help promote its clearance.

"If you have low levels of LDL, and thus, low levels of oxidized LDL, then CRP may be of benefit," Witztum said. "However, when there is an overwhelming accumulation of LDL, and thus oxidized LDL, in its attempt to help clear the toxic particle, the CRP may actually make things worse. It may cause more oxidized LDL to be taken up into macrophage scavenger cells, which in turn cause cholesterol accumulation a sort of 'Trojan horse'."

For the past 20 years, the Witztum lab at UCSD, in collaboration with UCSD professor of medicine Daniel Steinberg, M.D., Ph.D., has pioneered the role of oxidized LDL as a major contributing factor for the development of atherosclerosis. In particular, the Witztum lab has been studying immunological response to oxidiz
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Contact: Sue Pondrom
spondrom@ucsd.edu
619-543-6163
University of California - San Diego
9-Sep-2002