UCSD bioengineers have found a link between parallel alignment of “stress fibers” (red) in blood vessel cells and healthy levels in those cells of a protein called JNK. The white bar (lower right) represents 10 μm.
July 12, 2006 -- 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.
|This video of a team of UCSD Jacobs School of Engineering researchers shows how mechanical forces applied to blood vessel cells may reveal how atherosclerosis develops. Length: 1:13|
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 toment.
“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 directionality of blood vessel stretching.”
Cells that were stretched back and forth along one axis exhibited a healthy response: the level of JNK rose and quickly returned to basal levels as the cells also produced intracellularaligned perpendicular to the axis of stretching. However, when the researchers stretched cells in two directions simultaneously, they noted an unhealthy response: actin fibers oriented randomly and JNK concentrations rose to higher levels and remain elevated.
said Chien. “At the same time, the actin cytoskeleton of endothelial cells is somehow playing a key role in activating and deactivating JNK.”