Abstract 304: Chemokine Receptor CCR2 Mediates Monocyte Mobilization and Migration in Experimental Aneurysms
Abdominal aortic aneurysm (AAA) is a macrophage-driven vascular inflammatory disease. Chemokine receptor CCR2, a critical mediator of monocyte mobilization and migration, promotes AAA pathogenesis in hyperlipidemic mice following angiotensin II infusion. This study examined the role o CCR2 signaling in AAA formation in a mechanistically distinct experimental aneurysm model. AAAs were created in 10 week old male CCR2 knockout (KO) and wild type C57BL/6J mice via transient intra-aortic porcine pancreatic elastase (PPE) infusion. Aneurysm progression and aortic cellularity were evaluated using ultrasonography, histology and FACS analyses. In CCR2 KO mice, minimal aneurysmal enlargement was apparent following PPE infusion. Histologically, aortic medial elastin and smooth muscle cellularity were minimally degraded, and mural macrophage accumulation and angiogenesis were also significantly reduced compared to WT mice. Significantly fewer circulating and splenic inflammatory monocytes were identified via FACS analysis in KO mice, with a reciprocal increase in bone marrow monocyte cellularity. In in vivo monocyte migration assays, CCR2 deficiency was associated with a 60 -70% reduction in migration of intravenously transferred monocytes into aneurysmal aortae. In conclusion, targeted deletion of CCR2 in mice profoundly reduces mobilization of inflammatory monocytes from the bone marrow, while suppressing aneurysmal degeneration following PPE infusion. CCR2 signaling may represent an attractive target for therapeutic inhibition in medical management of AAA disease.
Author Disclosures: B. Xu: None. N. Fujimura: None. H. Xuan: None. J. Dalman: None. Y. Furisho: None. H. Tanaka: None. K. Glover: None. M. Rouer: None. K. Aoyama: None. S. Michie: None. R. Dalman: None.
- © 2014 by American Heart Association, Inc.