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Abdominal aortic aneurysms are more correlated with cigarette smoking than is any other vascular disease, and patients who smoke tend to have larger AAAs and those that expand more rapidly.

However, matrix metalloproteases typically associated with AAA development do not appear to play a role in smoking-induced dilatation, at least not according to an animal model presented by Dr. John Curci and his colleagues at the annual meeting of the Midwestern Vascular Surgical Society in September.

A total of 30 SvEv strain mice were exposed to tobacco smoke for 4 weeks; 23 nonexposed animals served as controls. At 4 weeks, all 53 animals were subjected to elastase perfusion (a procedure known to stimulate abdominal aortic aneurysm formation in mice).

Animals were sacrificed after elastase perfusion at either 2 weeks (10 mice from each group) or at 8 weeks (the remaining mice).

This research was originally presented by Dr. Amy Hackmann, Dr. Curci, and colleagues from Washington University in St. Louis.

Prior to sacrifice, repeat laparotomy and aortic diameter measurements were performed and blood was collected by cardiac puncture and RNA was extracted from the leukocyte fraction.

The aneurysmal section of the aorta then was harvested for RNA extraction and histologic analysis. Expression levels of two key matrix metalloproteases (MMP-9 and MMP-12) were assessed, according to the researchers.

There was no significant difference on initial aortic dilatation (at 2 weeks) between the smoke-exposed and control mice. However, the control mice appeared to stabilize, compared with the inhaled cigarette exposed mice, whose aortic diameter continued to increase beyond 2 weeks.

By 8 weeks post perfusion, aortic diameters were significantly different between the two groups: an average percentage change from preperfusion of nearly 170% in the smoke-exposed animals, compared with about 110% change in the controls.

Contrary to expectations, however, MMP-9 and MMP-12 expression levels from the aortic wall or circulating leukocytes were not found to be significantly different between cigarette-exposed and control mice.

"Somewhat surprisingly, the effect of smoking on aneurysms may be secondary to an impairment of the mechanisms of matrix repair rather than enhanced matrix injury," Dr. Curci said in an interview.

"This illustrates how this model now allows us to investigate the mechanisms of tobacco smoking on vascular pathology, which we hope will continue to offer new insights into the development of aneurysm disease," added Dr. Curci.

Matrix destruction in AAA has been determined to be caused by many of the same factors that play a role in smoking-induced emphysema, according to the researchers.

These factors include the metalloproteases MMP-9, MMP-12, as well as neutrophil elastase, reactive oxygen species, systemic proinflammatory mediators (such as interleukin and tumor necrosis factor), and smooth muscle cell apoptosis, according to the researchers.