Abstract 235: Macrophage Depletion Reduces Angiotensin Ii-induced Aortic Inflammation but Not Experimental Aneurysm Formation

Abstract

Massive mural macrophage infiltration is observed in experimental and clinical abdominal aortic aneurysm (AAA) disease. However, causational relationships, if any, between macrophage infiltration and aneurysm pathogenesis remain uncertain. This study examined the consequences of total and activated macrophage depletion on aneurysm formation and progression in the angiotensin II infusion, apolipoprotein E-deficient (Ang II/Apo E^-/-) AAA model. Mice were evaluated via serial in vivo aortic ultrasonography for 28 days during the Ang II infusion, and histology at sacrifice. In CD11b-diphtheria toxin (DT) receptor transgenic (DT⁺) Ang II/ApoE^-/- mice, DT injection failed to prevent aneurysm formation despite successful macrophage depletion. AAAs developed in 40% of DT⁺ Ang II/ApoE^-/- mice, a rate similar to littermate control, DT^- Ang II/ApoE^-/- receiving Ang II and DT. Similar results were observed when Ang II/Apo E^-/- mice were treated with folate receptor (FR) β immunotoxin (to deplete activated macrophages characterized by FRβ expression) compared with control toxin. Histologically, DT treatment in DT⁺ Ang II/ApoE^-/- mice reduced aortic CD68⁺ mural macrophages by 77% and 60% in mice with or without aneurysms, respectively. Similarly, activated macrophage depletion via FRβ immunotoxin resulted in a 33% and 50% reduction in mural CD68⁺ macrophages in mice with and without aneurysms, respectively. In conclusion, neither the total or activated mural macrophages appear to mediate aneurysmal aortic enlargement in the Ang II/ApoE^-/- AAA model.