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Atherosclerosis and its Mechanics

earch scientist Shunichi Usami, and post-doctoral fellow Roland Kaunas, now an assistant professor of biomedical engineering at Texas A&M University, isolated endothelial cells from the bovine aorta and grew them in culture flasks. They seeded the cells onto silicone rubber membranes that had been coated with a protein that allowed the cells to attach the way they do to underlying blood vessel tissue in the body. They then stretched the cells 10 percent of their length 60 times per minute to simulate the rhythmic flexing of an artery in response to heart beats.

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 intracellular actin fibers that were aligned 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.

"We're continually amazed at how quickly these cells can reorient these stress fibers when we change the direction of stretch," said Chien. "At the same time, the actin cytoskeleton of endothelial cells is somehow playing a key role in activating and deactivating JNK."

The tubular geometry of the straight part of arteries ensures that the cyclical rise and fall of blood pressure results in uniaxial stretch of arteries. However, the more complex geometry of artery branches promotes an unhealthy stretching of the blood vessel along more than one axis.

A second mechanical force, the so-called shear force of blood flowing through vessels, also influences the orientation of stress fibers in endothelial cells. A laminar flow of blood prompts stress fibers to orient in the healthy direction, while disturbed and low blood flows caused stress fibers to form in an unhealthy, random orientation. Chien's group i
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