Accelerated enlargement of experimental abdominal aortic aneurysms in a mouse model of chronic cigarette smoke exposure.
BACKGROUND
Cigarette smoking and pulmonary emphysema are strongly associated with abdominal aortic aneurysms (AAAs), but the biologic mechanisms linking these conditions are undefined.


METHODS
To determine if exposure to cigarette smoke influences formation and growth of experimental AAAs, 129/SvEv mice were acclimated to daily cigarette smoke exposure for 2 weeks followed by transient elastase perfusion of the abdominal aorta to induce aneurysmal degeneration. Smoking was continued for intervals of either 2 or 12 weeks (8 mice per group). Nonsmoking 129/SvEv controls (n = 29) underwent elastase perfusion and followup evaluation at the same time intervals. In all animals, abdominal aortic diameter (AD) was measured to determine interval increases in AD (Delta AD), with AAAs defined as a Delta AD > 100%.


RESULTS
Preperfusion and immediate postperfusion ADs were not significantly different between experimental groups. Aneurysmal dilatation was present 2 weeks after elastase perfusion in both smoking mice and nonsmoking controls, with no significant difference in final AD (mean +/- SEM: smoking, 1.23 +/- 0.11 mm versus nonsmoking, 1.22 +/- 0.05 mm). There were also no differences in the overall extent of aortic dilatation (Delta AD smoking, 136 +/- 24% versus nonsmoking, 138 +/- 10%), or the incidence of AAAs (smoking, 75% versus nonsmoking, 79%). Although all animals had developed AAAs by 12 weeks after elastase perfusion, the overall extent of aortic dilatation was 50% greater in smoking mice compared with nonsmoking controls (Delta AD smoking, 204 +/- 23% versus nonsmoking, 135 +/- 17%; p < 0.05).


CONCLUSIONS
Short-term exposure to cigarette smoke did not alter initial development of experimental AAAs, but chronic smoke exposure was associated with a substantial increase in the late progression of aneurysmal dilatation. This novel combination of in vivo experimental models offers a new approach to investigate mechanisms by which cigarette smoking promotes aneurysmal degeneration.
Buckley
Celine
C
Department of Surgery, Section of Vascular Surgery, Washington University School of Medicine, St Louis, MO 63110, USA.
Wyble
Charles W
CW
Borhani
Martin
M
Ennis
Terri L
TL
Kobayashi
Dale K
DK
Curci
John A
JA
Shapiro
Steven D
SD
Thompson
Robert W
RW
D000818:Animals; D001012:Aorta, Abdominal / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000209:etiology*; D004106:Dilatation; D008297:Male; D051379:Mice; D010196:Pancreatic Elastase / Q000494:pharmacology; D010477:Perfusion; D011656:Pulmonary Emphysema / Q000209:etiology; D012906:Smoke / Q000009:adverse effects*; D013997:Time Factors; D014026:Nicotiana
D012906:Smoke; D010196:Pancreatic Elastase