28.08 The Pro-Resolving Lipid Mediator Maresin 1 (MaR1) Attenuates Abdominal Aortic Aneurysm Formation

C. T. Elder1, G. Lu1, G. Su1, A. K. Sharma1, A. Mast1, G. R. Upchurch1  1University Of Florida,Department Of Surgery,Gainesville, FL, USA

Introduction:  Formation of abdominal aortic aneurysms (AAA) is a multifactorial process and is characterized by inflammation of the aortic wall. Maresin 1 (MaR1) is an endogenous pro-resolving lipid mediator derived from docosahexanoic acid, an ω-3 polyunsaturated fatty acid, and is involved in the resolution phase of acute inflammation. We hypothesized that treatment with exogenous MaR1 would attenuate experimental murine AAA formation.

Methods:  Abdominal aortic aneurysms were induced in C57BL/6 (wild-type; WT) mice (n=4 per group) using an established topical elastase model. Mice were treated with MaR1 (100 ng/mouse for each dose) or vehicle via intraperitoneal injection on days 1, 3, 5, and 7 post AAA induction. On day 14, abdominal aortas were harvested for phenotypic evaluation. 

Results:  Mean abdominal aortic dilation was 131% ± 16 for vehicle treated mice as compared to 88% ± 7 for MaR1 treated mice (p = 0.003). Decreased inflammatory changes were noted on gross phenotypic examination for MaR1 treated mice as compared to vehicle treated mice. 

Conclusion:  The present results demonstrate that systemic administration of MaR1 attenuates abdominal aortic aneurysm formation in mice. Decreased inflammatory phenotypic changes suggest this attenuation is mediated through the pro-resolving effects of MaR1 and represent a potential future target in the treatment of AAA.