Abstract 712: Elastin Derived Peptides Augments Abdominal Aortic Aneurysm Formation

Abdominal aortic aneurysm AAA is a chronic dilatation of the abdominal aorta. It is a potentially life threatening disease as it develops asymptomatic and is often first discovered at the time of rupture. One key element in AAA formation is degradation of the elastin fibers in the aortic wall. When elastin is degraded small bioactive elastin derived peptides (EDPs) are released into the circulation. These EDPs affect vascular smooth muscle cells in the aortic wall and attract monocytes to the aortic wall resulting in further degradation of elastin. We hypothesize that the level of circulating elastin derived peptides (EDPs) augments AAA expansion and that inhibition of circulating EDPs will inhibit AAA expansion. We tested the hypothesis in an elastase induced aneurysm murine model by applying synthetic EDPs or scrambles peptides and measure the AAA size. In addition, EDP-neutralizing antibody or control IgG was given to angiotensin II induced AAA in ApoE-/- mice and AAA size was determined 28 days later. Fourteen days after elastase infusion the abdominal aortic diameter was significantly increased in the EDP treated group when compared to the scramble peptid treated control group (1.33±0.07 vs. 1.13±0.06 mm, n=17-19, p<0.05). Inhibition of circulating EDPs by EDP neutralizing antibodies when compared to IgG controls showed a clear trend toward decreased AAA expansion based on outer aortic diameter (1.4 ±0.1 vs. 2.2 ±0.4 mm, n=8-9, p=0.059) and wet weights of the abdominal aorta (median: 9.2 vs. 22.1 mg, n=7-9, p=0.07) 28 days after angiotensin II infusion in ApoE-/- mice. In the aneurysmal wall of the mice treated with elastin neutralizing antibody, there was less ruptured elastin, and there was significantly fewer infiltrating of CD45 positive cells, while CD206 positive anti-inflammatory M2 macrophages were significantly augmented when compared to IgG treated controls (n=7-9).In conclusion, EDPs augment abdominal aortic aneurysms. Thus, inhibition of circulating EDPs shows great potential against AAA expansion.