Do Neutrophils Play a Role in Abdominal Aortic Aneurysms?

Identification of the early factors underlying the deterioration and swelling of the aortic wall could lead to new treatments to prevent aneurysms from developing in high-risk patients, according to Gilbert R. Upchurch Jr., M.D., leader of two studies undertaken with his colleagues at the University of Michigan, Ann Arbor.

The discovery of ways to curb neutrophil infiltration of the vascular wall may be the route to prevention, he said.

In the first study, Dr. Upchurch and his colleagues treated mouse aortas with elastase to induce aneurysms. A mean aortic diameter increase of 104% was seen in control animals, and 67% developed abdominal aortic aneurysms (AAAs) after 14 days.

In contrast, mice also treated with injections of antineutrophil antibody (anti-PMN) had a mean aortic diameter increase of 42%, with only 8% developing AAAs.

The injection of anti-PMN was also found to significantly decrease the number of circulating neutrophils, compared with normal controls (Circulation 2005;112:232-40).

In the second study, elastase-perfused rat aortas showed a significant increase in L-selectin levels, which was coupled to a significant increase in neutrophil recruitment to the aorta, followed by aneurysm development (Circulation 2005;112: 241-7). L-selectin is one of a family of adhesion molecules that promote leukocyte capture to sites of inflammation. Elastase perfusion of L-selectin-knockout mice resulted in significantly smaller aortic diameters (88% vs. 123% in the controls) and only 38% developed AAAs, compared with 67% in wild-type mice. The decrease in diameter and number of aneurysms was associated with decreased neutrophil infiltration into the aortic wall of the knockout mice.

The authors of this study point out two key limitations: Only a partial reversal of the aortic aneurysm phenotype was seen in the knockout mice, and it is unknown whether the elastase induction model can be applied to AAAs in humans. However, the studies do provide impetus for future research.

"The present communications ... lift the level of discourse on the role of PMN to a new plateau," commented M. David Tilson III, M.D., of the department of surgery, Columbia University, New York, in an accompanying editorial (Circulation 2005;112:154-6).

"As other investigators are intensifying the search for AAA susceptibility genes in humans, the regulation of PMN recruitment becomes a new candidate for molecular analysis," Dr. Tilson concluded.