Abstract 485: Effect of Bone Marrow Transplantation on Aortic Inflammatory Disease and Accelerated Atherosclerosis
In ApoE-/- mice Ang II infusion leads to vascular inflammation resulting in the formation of aortic aneurysms and accelerated atherosclerosis. In order to elucidate the role of hemopoetic cells in these pathologies, bone marrow transplant (BMT) has been utilized. However, if BMT is used, it is critical that we fully understand the effect of BMT on aortic inflammatory disease and atherosclerosis. In this study we used Ang II to investigate the effects of bone marrow transplant on aortic inflammatory disease and accelerated atherosclerosis.
ApoE-/- mice (12wk age) were either lethally irradiated (2x 5Gy) and reconstituted with ApoE-/- bone marrow (1x10-6 cells) or non-irradiated. . BMT mice and non-irradiated littermates were treated with Ang II (0.8mg/kg/day) to induce aortic inflammation and accelerate atherosclerosis. After 14 days of treatment mice were culled and the aorta and aortic root harvested. AngII infusion in non-irradiate mice resulted in a 33% incidence in aortic aneurysm, however, in BMT mice no aneurysms were observed. Ang II infusion lead to an increase in atherosclerosis with a significant increase in inflammatory cell infiltration observed. Irradiation resulted in a significant decrease in Ang II-induced accelerated atherosclerosis (0.049±0.003 vs. 0.037±0.016; P<0.05; non-irradiated vs. irradiated) and a significant reduction in macrophage infiltration (0.018±0.003 vs. 0.007±0.002; P<0.05; non-irradiated vs. irradiated). However, in order to achieve a similar incidence of aortic aneurysms in BMT mice as observed in non-BMT mice treated with 0.8 mg/kg/day Ang II, the dose of Ang II had to be increased to 3mg/kg/day. A similar result was observed in atherosclerosis studies, with a dose of 3mg/kg/day required to induce comparable levels of macrophage infiltration and plaque size to those in non-BMT mice treated with a dose of 0.8mg/kg/day.
In conclusion, BMT resulted in a significant decrease in AngII-induced accelerated atherosclerosis and a reduction in Ang II-mediated aortic inflammation. Interestingly, BMT mice had a significant reduction in inflammatory cell infiltration compared with non-irradiated littermates indicating that the reduction maybe due to an alteration in inflammatory cell recruitment after BMT.
Author Disclosures: G. Douglas: None. J. Patel: None. A. Hale: None. K.M. Channon: None.
- © 2014 by American Heart Association, Inc.