Abstract 19204: IL-10 Accentuates Ascending Aortic Aneurysm Formation in a Novel Model Using Beta-Aminopriopionitrile
Introduction: Ascending aortic aneurysms are characterized by elastin fragmentation. The goal of the current study is to increase the penetrance in a model of ascending aortic aneurysm formation using β-aminopropionitrile (BAPN) and to determine if IL-10 plays a role in ascending aneurysm formation.
Methods: Wild-type male mice (C57BL/6; age 8-12 weeks) underwent Angiotensin II infusion (2000 ng/kg/min) using osmotic pump for 28 days with high fat western diet and either normal drinking water or water supplemented with 4% BAPN (n=25/group). Aortic diameter was measured by ultrasonography before Angiotensin II infusion and at days 14 and 28 following pump insertion.
In separate studies, wild-type male and female mice (C57BL/6; age 8-12 weeks) were fed high fat Western diet and underwent Angiotensin II infusion (2000 ng/kg/min) accompanied by 4% BAPN treatment for 28 days (n=25 mice/group).
Finally, a separate group of wild-type and IL-10 KO male mice underwent Angiotensin II infusion (2000 ng/kg/min), 4% BAPN treatment, Western diet treatment, and were followed for 28 days (n=15/group). For each set of studies, animals were followed by ultrasound and harvested at 28 days following infusion. Aortic diameter was measured and blood and tissue were harvested. Statistical comparisons were performed with statistical significance of 0.05.
Results: Wild-type male mice treated with BAPN demonstrated worse mortality due to aneurysm rupture and higher incidence of aneurysm formation (p<0.05, 55% penetrance, n=25/group). Wild-type male and female mice did not exhibit differences in ascending aneurysm rupture or formation consistent with human ascending aneurysm disease (p=0.45, n=25/group). Finally, compared to IL-10 KO demonstrated worse mortality due to rupture and a higher incidence of ascending aneurysm formation (p<0.05, 75% penetrancen=15/group).
Conclusions: BAPN treatment increased the incidence of ascending aortic aneurysm formation but not in a gender-dependent manner, suggesting BAPN can increase the penetrance of ascending aneurysm formation in wild-type mice. IL-10 KO mice demonstrated greater aneurysm formation and higher mortality from rupture, indicating that IL-10 may be important in attenuating aneurysm formation and rupture.
Author Disclosures: M. Salmon: None. A. Fashandi: None. R.B. Hawkins: None. M. Spinosa: None. A.K. Sharma: None. G.R. Upchurch: None. G. Ailawadi: None.
- © 2016 by American Heart Association, Inc.