Abstract 713: Angiotensin 1-7 Suppresses Experimental Abdominal Aortic Aneurysms

Objectives: Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease, the pathogenesis of which remains incompletely defined. We and others have demonstrated the critical role of angiotensin (Ang) II and its receptor AT1 in experimental AAAs. Although Ang 1-7 and its receptor Mas counteract many AT1 functions, the role of the Ang 1-7/Mas pathway has not been studied in AAAs. This study evaluated the influences of Ang 1-7 and Mas on experimental AAAs. Methods: AAAs were created in male C57BL/6J mice via porcine pancreatic elastase (PPE) infusion. Mice were treated with Ang 1-7 (0.5 mg/kg/day via s.c) or vehicle starting immediately prior to, or 4 days following, PPE infusion. Additional mice were co-treated with Ang 1-7 and the Mas receptor antagonist A779 (0.5 mg/kg/day) beginning immediately prior to PPE infusion. Influences on AAAs were evaluated by serial ultrasound imaging and histology. Results: Figure summarizes major results. In ultrasound imaging, at 14 days Ang 1-7 treatment initiated immediately following aneurysm creation substantially suppressed aortic enlargement as compared to vehicle treatment. Histologically, Ang 1-7 treatment was associated with attenuation of aortic medial elastin and smooth muscle cell depletion, mural macrophage, CD4 + , CD8 + T and B cell density and neoangiogenesis. Co-treatment with Ang 1-7 receptor Mas antagonist A779 “rescued” the aneurysm phenotype. Additionally, Ang 1-7 treatment initiated even 4 days following AAA creation was still effective in limiting further aneurysmal enlargement and pathologic evolution. Conclusions: Ang 1-7 treatment, initiated either at, or up to 4 days following, AAA initiation limits further progression of experimental AAAs. This inhibitory effect seems likely related to activation of the Mas receptor. These results suggest that either Ang 1-7 or alternative Mas receptor agonists may have clinical utility in suppressing progression of early AAA disease.