Abstract 11574: Orally Administered Eicosapentaenoic Acid Attenuates Vascular Oxidative Stress and the Development of Angiotensin-ll Induced Aortic Aneurysm Formation
Background: Abdominal aortic aneurysm (AAA) is a common but life-threatening disease among the elderly, for which no effective medical therapy is currently available. Recently, omega-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were shown to have direct anti-inflammatory effects independent of change in lipid profiles. Chronic infusion of angiotensin II (AngII) augments abdominal aortic aneurysm (AAA), which is associated with medial macrophage accumulation and matrix metalloprotease (MMP) activation. The purpose of this study was to define whether omega-3 fatty acids would attenuate the development of AAA.
Methods: Male apolipoprotein-E deficient mice were fed a diet with 5% EPA (AngII+EPA group, n=10) or without fish oil (AngII group, n=10) for 5 weeks. After 1 week of feeding, mice were infused with AngII (1000 ng/kg per minute) for 4 weeks. Saline-treated mice were served as control (n=10).
Results:An increase in systolic blood pressure was observed equivalently in both groups. AngII infusion for 4 weeks induced AAA formation in 80% of the AngII group; however, oral administration of EPA strikingly decreased the incidence of AAA by 30% (p<0.01) (external diameters; 2.40±0.74 [AngII] vs. 1.54±0.70 [AngII+EPA] vs. 0.96±0.05 [Saline], p<0.01, respectively). MMP-2 and MMP-9 detected by zymographic analysis and inflammatory cytokines such as TNF-α and MCP-1 measured by quantitative PCR were significantly reduced in the AngII+EPA group (p<0.01). The In situ dihydroethidium staining of AAA tissue for 1 week after AngII-infusion showed that reactive oxygen species (ROS) in vessel walls, ecpecially in smooth muscle cells was significantly reduced by EPA treatment (p<0.01). In vitro experiments, pretreatment of EPA (10-100μ M) significantly suppressed AngII-induced ROS generation by 40 % and apoptosis in cultured smooth muscle cells, and also decreased AngII-induced inflammatory cytokines in peritoneal macrophages.
Conclusions: EPA may potentially reduce experimental AAA development possibly by inhibiting proteolysis, inflammation, and oxidative stress. EPA may offer an additional method to pharmacologically inhibit AAA
- © 2012 by American Heart Association, Inc.