Abstract 35: Macrophage Depletion Limits Experimental Aneurysm Progression
Macrophage activity mediates aortic aneurysm pathogenesis. Aortic mural macrophage density, and activation status, may alter progression of existing abdominal aortic aneurysms (AAAs). We examined the consequences of macrophage depletion on aneurysm progression using the porcine pancreatic elastase (PPE) AAA model. Following PPE infusion, aortic diameter enlarged progressively through 14 days as measured via serial transabdominal ultrasound examinations in control mice. Total macrophage depletion via diphtheria toxin (DT) injection, initiated prior to PPE infusion in CD11b-diphtheria toxin receptor (DTR) transgenic mice, abrogated aortic enlargement. Initiation 4 days following PPE infusion promoted AAA regression. In separate experiments, depletion of activated macrophages, those characterized by folate-receptor β (FRβ) expression, was accomplished via FRβ-directed immunotoxin treatment in C57BL/6 mice. FRβ immunotoxin limited AAA progression in this construct. Both DT injection in DTR-transgenic mice, and FRβ immunotoxin treatment in C57BL/6 mice, preserved medial smooth muscle cellularity and elastin content, and reduced mural inflammation and neovessel formation on histopathologic analysis. In conclusion, modulation of mural macrophage cellularity may represent an effective method of non-surgical AAA disease management.
- © 2013 by American Heart Association, Inc.