Abstract 305: Myeloid Cell-Specific VEGF-A Deletion Inhibits Experimental Abdominal Aortic Aneurysms

Abstract

Mural macrophage infiltration and angiogenesis are histopathological hallmarks of abdominal aortic aneurysms (AAA). Macrophages produce angiogenic cytokine VEGF-A in many pathologic settings. It is not known whether VEGF-A produced by macrophages plays a role in aneurysm disease. In this study, we generated myeloid cell-specific VEGF-A conditional knockout (CKO) mice using the Cre/LoxP technology, and evaluated the influences of myeloid VEGF-A ablation on the formation and progression of aneurysm disease. AAAs were created in 10-12 week old male CKO and wild type (WT) mice via intra-aortic porcine pancreatic elastase (PPE) infusion and assessed by serial ultrasound measurements of aortic diameters followed by histology at sacrifice. Following PPE infusion, aneurysmal degeneration was significantly blunted in CKO mice. Histologically, medial elastin fragmentation, macrophage density, and mural angiogenesis were significantly diminished in the aortae of CKO mice compared to those in WT mice. Additionally, myeloid VEGF-A deletion caused marked reduction in peritoneal CD115-positive or F4/80-positive macrophages following thioglycollate injection. In conclusion, targeted deletion of VEGF-A in myeloid cells suppresses aneurysm initiation and progression in association with reduced mural macrophage accumulation and angiogenesis.