Abstract 282: Pattern of Development of Abdominal Aortic Aneurysms Induced by Angiotensin In Hypercholesterolemic Mice
Background Understanding the pattern of development of abdominal aortic aneurysms (AAA) may help optimize translational research strategies. Thus we sought mechanistic insight on the pattern of AAA evolution in apolipoprotein E -/- mice.
Methods Fifty-nine mice underwent a 4-week pump-mediated infusion of saline (controls; n=13) or 1500 ng/kg/min of AngII (n=46), and AAA development was tracked via in vivo serial ultrasound imaging. We adjusted for hemodynamic covariates in the mixed logistic regression model for AAA occurrence in relation to time.
Results The incidence of intact AAA in AngII infused mice was 59% (27/46) of which 55.6% (15/27) were small AAA and 44.4% were large AAA (1.2-1.5 vs. >1.5x baseline diameter, respectively). The incidence of rupture was 22% (10/46). All large aneurysms and most ruptures occurred within the first week of AngII exposure. Subsequent aneurysms were small and evolved in the second week of AngII infusion. The overall effect of time was statistically significant (p<0.001) (Figure). When compared to day 7 of the study period, there was no decrease in the log odds of AAA occurrence by day 14 (-0.234, p = 0.65). However, compared to 21 and 28 days into AngII infusion, the log odds of an AAA occurrence decreased by -9.07 (p< 0.001) and -2.35 (p= 0.04), respectively (Figure).
Conclusions These are the first formal estimates of the odds of AAA occurrence vis-à-vis time in the context of a consistent pattern of AAA development in this mouse model of AngII-induced AAA. They occur in the first (large AAA) and second (small AAA) weeks of AngII infusion, and the odds of occurrence diminish thereafter. These findings provide guidance for experimental strategies.
- © 2013 by American Heart Association, Inc.