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UCSD team identifies potential role of CRP in development of antherosclerosis

Another piece of the complex puzzle of how inflammation is involved in heart attacks and strokes has been discovered by researchers at the University of California, San Diego (UCSD) School of Medicine.

Their findings demonstrate that C-reactive protein (CRP) binds to oxidized low density lipoprotein (LDL), implicating the interaction of CRP and oxidized LDL as a potential trigger for the cascade of events leading to atherosclerosis. This form of artery disease is characterized by the buildup of fatty deposits and chronic inflammation along the artery wall, eventually leading to heart attack.

Published in the online edition of Proceedings of the National Academy of Sciences (PNAS) the week of Sept. 9, 2002, the study by the UCSD researchers pinpoints how CRP attaches itself to oxidized LDL, the so-called "bad cholesterol" that accumulates in the artery wall and generates atherosclerotic plaques. LDL is the major cholesterol carrying particles. When they enter the artery wall from the circulation, they are believed to be modified by oxidation. It is this "oxidized LDL" that is thought to be the culprit leading to inflammation and cholesterol accumulation.

"Our study points out that CRP is not merely a marker of future cardiovascular events, as most people believe, but it actually binds to oxidized LDL and apoptotic or dying cells, giving it a potential role in development or modulation of atherosclerosis, as well as in other inflammatory disease," said Mi-Kyung Chang, M.D., an assistant project scientist and the first author of the paper in PNAS.

In the new studies, the UCSD team showed that CRP binds to oxidized LDL through the recognition of phosphocholine, a part of an oxidized molecule on the surface that is exposed when LDL undergoes oxidation.

Noting that there is an accumulation of dead and dying cells (apoptotic cells) in atherosclerotic lesions and that these cells are under increased oxidative stress, the UCSD
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Contact: Sue Pondrom
spondrom@ucsd.edu
619-543-6163
University of California - San Diego
9-Sep-2002


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