Atherosclerotic narrowing and hardening of coronary arteries typically appear first at vessel branches, and a study in the October issue of Cellular Signalling reports that the type of mechanical stretching found at those branches activates a cellular protein known to damage cells. The report is the first to link mechanical forces with structural and biochemical changes in blood vessel cells that could explain why atherosclerotic lesions form preferentially at branches of coronary arteries.

The findings, which are currently available online at the journal's Website, were reported by a team of scientists at the University of California, San Diego as part of an ongoing effort to understand how mechanical forces affect the health of cells that line arteries.

The cellular protein in question is called JNK, which is short for c-jun N-terminal kinase. The protein is a key barometer of outside stresses on a variety of cell types. Researchers are examining the role of JNK in many diseases because it regulates the expression of genes involved in programmed cell death, tumor genesis, and other stress responses.

Atherosclerosis, the collection of deposits such as cholesterol along artery walls, accounts for nearly 75 percent of deaths from cardiovascular disease. Most drugs to treat atherosclerosis influence the levels of cholesterol and other lipids in the blood, but the UCSD researchers suspect that understanding the role of mechanical forces acting on blood vessel cells may help to design better approaches to treatment.

"We've known for decades that atherosclerotic lesions develop preferentially at vessel branches rather than along unbranched vessels, but we've not been able to identify the biochemical events that trigger formation of the lesions," said Shu Chien, director of the Whitaker Institute of Biomedical Engineering at UCSD. "We now have identified a possible smoking gun: activation of JNK, which is dependent on the directi
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Contact: Rex Graham
ragraham@ucsd.edu
858-822-3075
University of California - San Diego
12-Jul-2006