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Why do aneurysms form? New studies suggest leading role for white blood cells

rry some of these enzymes, called matrix metalloproteinases and chemokines, which help them attack invaders," says Upchurch. "We wanted to see what the role of neutrophils was in the early stages of aneurysm formation and the progression of the aneurysm."

Upchurch and his colleagues performed one of the studies using mice that had been treated with an antibody that attacked their neutrophils and kept the levels of the cells circulating in the blood artificially low. They applied the enzyme elastase to the aortas of these mice and normal control mice. Two-thirds of the control mice developed an aneurysm at the injury site within two weeks, with an aneurysm area twice the normal size on average. In contrast, only 8 percent of the neutrophil-deficient mice developed an aneurysm and those that did develop were much smaller.

The researchers also looked at the levels, activity and production of enzymes before and during the aneurysm formation. For two of the matrix metalloproteinases, there was no difference between the two kinds of mice. For one called MMP-8, though, much less was produced in the neutrophil-deficient mice. But the researchers performed more experiments that showed that the lack of MMP-8 was not enough by itself to keep aneurysms from forming.

"Something else must be at work," says Upchurch, "and we're trying to find out what that is."

In the second study, the researchers looked at L-selectin, a protein on the surface of neutrophils that allow them to attach to tissue. They studied L-selectin production in the aortas of rats that had been injured with elastase or exposed to control conditions. They also studied mice that had been genetically altered by U-M researchers to lack the gene for L-selectin, and normal comparison mice.

In general, the rat aortas exposed to elastase had far higher levels of L-selectin in the days immediately after the injury. The L-selectin-deficient mice had significantly smaller aneurysms
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Source:University of Michigan Health System


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