Effect of irradiation and bone marrow transplantation on angiotensin II-induced aortic inflammation in ApoE knockout mice. (September 2018)

• Record Type: Journal Article
• Authors: Patel, Jyoti; Douglas, Gillian; Kerr, Alastair G.; Hale, Ashley B.; Channon, Keith M.
• Is Part Of: Atherosclerosis. Volume 276(2018)
• Page Start: 74
• Page End: 82
• Publication Date: 2018-09
• Subjects: Bone marrow transplantation -- Angiotensin II -- Aneurysm -- Monocyte; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2018.07.019
• Languages: English
• ISSNs: 0021-9150

Abstract

Abstract: Background and aims: Angiotensin II (Ang II) infusion promotes the development of aortic aneurysms and accelerates atherosclerosis in ApoE −/− mice. In order to elucidate the role of hematopoietic cells in these pathologies, irradiation and bone marrow transplantation (BMT) are commonly utilized. The aim of this study was to investigate the effects of irradiation and BMT on abdominal and thoracic aortic aneurysm formation and acute leukocyte recruitment in the aortic root and descending aorta, in an experimental mouse model of aortic aneurysm formation. Methods: ApoE −/− mice were either lethally irradiated and reconstituted with ApoE −/− bone marrow or non-irradiated. Following engraftment, mice were treated with Ang II to induce aortic inflammation and accelerate atherosclerosis. Results: Ang II infusion (0.8 mg/kg/day) in BMT mice resulted in reduced aortic aneurysms and atherosclerosis with decreased leukocyte infiltration in the aorta compared to non-BMT mice, when receiving the same dose of Ang II. Furthermore, the reduced aortic infiltration in BMT mice was accompanied by increased levels of monocytes in the spleen and bone marrow. A dose of 3 mg/kg/day Ang II was required to achieve a similar incidence of aneurysm formation as achieved with 0.8 mg/kg/day in non-BMT mice. Conclusions: This study provides evidence that BMT can alter inflammatory cell recruitment in experimental mouse models of aortic aneurysm formation and atherosclerosis and suggests that irradiation and BMT have a considerably more complex effect on vascular inflammation, which should be evaluated. Highlights: Ang II infusion in bone marrow transplanted mice results in fewer aneurysms with decreased aortic leukocyte infiltration. Reduced aortic infiltration in bone marrow transplanted mice is accompanied by increased levels of monocytes in the spleen. Irradiation and bone marrow transplantation has complex effects on vascular inflammation which should be evaluated.