Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA318

Poster Communications

Elastin derived peptides augments abdominal aortic aneurysm formation

J. Stubbe1,2, N. Bjørnes1, P. Tu Quyen1, A. Kurtzhals1, S. Griepke Dam Nielsen1, L. Melhotl Rasmussen2, J. Sanddal Lindholt2

1. University of Southern Denmark, Odense C, Denmark. 2. Center for Individualized Medicine in Arterial Diseases (CIMA), Odense University Hospital, Odense, Denmark.


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 to the circulation. These EDPs affect vascular smooth muscle cells in the aortic wall and attract monocytes to the aortic wall leading to 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. Nine weeks old C57bl/6J male mice were anesthetized i.p. with a mixture of ketamine (100 mg/kg) and xylazine (10mg/kg) and AAA was induced by intraluminal elastase infusion in the infrarenal aorta at the day of surgery and every third day, mice were given synthetic EDPs or scrambles peptides (SC) i.v. until termination at day 14. In addition, 10-12 week old male ApoE-/- mice were anesthetized with isoflurane gas and osmotic mini-pumps filled to release angiotensin II (1µg/kg/min) were implanted subcutaneously to induce AAA formation over a period of 28 days. Mice were given anti-elastin neutralizing antibody or control IgG i.p. once a week during the experimental period. AAA size was determined as by subtracting baseline outer aortic diameter from maximal abdominal aortic diameter at the time of termination. At termination, mice were fixed by systemic perfusion of 4% paraformaldehyde and aneurysms were embedded in paraffin for morphological analyses. Fourteen days after elastase infusion the maximal abdominal aortic diameter was significantly increased in the EDP treated group when compared to the SC treated 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 maximal 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 elastin neutralizing antibody treated group elastin was more preserved when compared to the IgG treated group (elastin degradation score (1-4): 2.0 ± 0.4 vs. 3.4 ± 0.4, n= 8-9, p<0.05). The number of CD45 positive leukocytes in the aneurysmal wall was significantly higher in the IgG treated mice when compared to the elastin neutralizing antibody treated group, while no obvious differences were detected in the number of CD206 positive anti-inflammatory M2 macrophages between groups. In conclusion, EDPs augment abdominal aortic aneurysms. Thus, inhibition of circulating EDPs shows great potential against AAA expansion.

Where applicable, experiments conform with Society ethical requirements