Effect of irradiation and bone marrow transplantation on angiotensin II-induced aortic inflammation in ApoE knockout mice

Abstract

Background and aimsAngiotensin 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.MethodsApoE−/− 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.ResultsAng 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.ConclusionsThis 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.

Redox Regulation of Cardiac ASK1 (Apoptosis Signal-Regulating Kinase 1) Controls p38-MAPK (Mitogen-Activated Protein Kinase) and Orchestrates Cardiac Remodeling to Hypertension

“…We used a model of hypertension induced by Ang II in C57Bl/6J male mice to assess this. We selected a moderate concentration that induces hypertension (0.8 mg/[kg·d] Ang II), 30 rather than a subpressor dose (eg, 0.288 mg/[kg·d]) 31 or one more associated with sudden cardiac death (eg, >2 mg/[kg·d]). Ang II significantly increased mRNA expression of the hypertrophic markers Nppa , Nppb , and Myh7 .…”

Crucial role of hematopoietic <i>JAK2</i> V617F in the development of aortic aneurysms

“…10 Ang II (1900 ng/kg per min) or saline was continuously infused for 4 weeks. 11,12 Ultrasound imaging and determination of aortic aneurysms…”

“…It has been reported the incidence of rupture of AAs is 21.3 per 100,000 people in the general population with a mortality of 85-90%. 12 Thus, it is important to stratify the risk of AA rupture, and to discover a novel mechanism for the formation and progression of AAs. It is known that circulating inflammatory cells play important roles in the development of AAs, accompanied by the secretion of various inflammatory factors such as cytokines and chemokines.…”

Angiotensin II Infusion Leads to Aortic Dissection in LRP8 Deficient Mice

“…Interestingly, none of the LRP8 −/− mice that received LRP8 +/+ bone marrow developed aortic dissections, while 2 out of 10 LRP8 +/+ mice that received LRP8 −/− bone marrow did. These results indicate that, despite the fact that irradiation is known to limit aneurysm formation and rupture [ 18 ], myeloid immune cells may play a major role in the formation of aortic dissection that was observed in LRP8 −/− mice infused with AngII.…”