Abstract 400: Protective Effects of CCR2 Deficiency on Ascending Aortic Aneurysm Formation Are Not Mediated via MCP-1
Background and Objective: Infusion of AngII into hyper- and normocholesterolemic mice leads to formation of aneurysms in the ascending aorta. Aneurysms in this region have markedly different pathology from those formed in the abdominal aorta. We have demonstrated previously that deficiency of the chemokine receptor, CCR2, attenuated ascending aortic aneurysm formation in hypercholesterolemic mice. The purpose of this study was to define whether deficiency of CCR2 also attenuated AngII-induced ascending aortic aneurysms in normolipidemic mice. Furthermore, we also determined whether the effects were attributable to its primary ligand, MCP-1.
Methods and results: Male C57BL/6, CCR2-/- and MCP-1-/- mice (The Jackson Laboratory, Bar Harbor, ME) were fed a normal diet. Mice were infused with either saline or AngII (1,000 ng/kg/min; N=20/group) subcutaneously via osmotic mini-pump for 28 days. Systolic blood pressure (SBP) was measured by a tail cuff-based technique. AngII increased SBP significantly and equivalently in all genotypes relative to saline-infused mice (P<0.05). Serum MCP-1 concentration was measured by ELISA. As expected, MCP1-/- mice had no measurable MCP-1; while CCR2-/- mice had a 10 fold increase compared to C57BL/6 mice (P<0.001). En face arch and ascending aortic areas were measured. AngII infusions significantly increased aortic areas compared to saline infused mice (P<0.001) in all genotypes. Although AngII caused similar aortic dilations in C57BL/6 and MCP1-/- mice, deficiency of CCR2 attenuated aortic expansion to the same extent as previously described in hypercholesterolemic mice (P<0.001) .
Conclusion: CCR2 reduces AngII-induced ascending aortic aneurysm formation in normolipidemic mice, although not via activation through MCP-1.
- © 2012 by American Heart Association, Inc.