Moran, CS and Jose, RJ and Moxon, JV and Roomberg, A and Norman, PE and Rush, C and Korner, H and Golledge, J, Everolimus limits aortic aneurysm in the apolipoprotein E-deficient mouse by downregulating C-C chemokine receptor 2 positive monocytes, Arteriosclerosis, Thrombosis, and Vascular Biology, 33, (4) pp. 814-821. ISSN 1079-5642 (2013) [Refereed Article]
Copyright 2013 American Heart Association
Objective: We aimed to determine the effect of mechanistic target of rapamycin inhibitor everolimus on abdominal aortic aneurysm within the angiotensin II (A2)-infused apolipoprotein E–deficient mouse model.
Approach and Results: Abdominal aortic aneurysm was induced via subcutaneous infusion of A2. Flow cytometry demonstrated increased circulating and aortic C-C chemokine receptor 2 (CCR2) monocytes during A2 infusion. The number of CCR2 monocytes present within the aorta was positively correlated with suprarenal aortic diameter. Simultaneous infusion of everolimus via a second subcutaneous osmotic micropump inhibited A2-induced aortic dilatation. Using flow cytometry and Western blot analysis, decreased aortic dilatation was associated with reduced development of CCR2 bone marrow monocytes, fewer numbers of circulating CCR2 monocytes, and lower aortic CCR2 concentration. In vitro, everolimus inhibited A2-stimulated production of interferon (IFN)-γ and IFNγ-induced CCR2 expression in apolipoprotein E–deficient mouse bone marrow monocytes. Further, everolimus diminished IFNγ/lipopolysaccharide-stimulated M1 polarization in apolipoprotein E–deficient mouse bone marrow monocyte–differentiated macrophages.
Conclusions: Systemic administration of everolimus limits aortic aneurysm in the A2-infused apolipoprotein E–deficient mouse model via suppressed development of bone marrow CCR2 monocytes and reduced egress of these cells into the circulation.
|Item Type:||Refereed Article|
|Keywords:||aneurysm, aorta, apolipoprotein E-null mouse, CCR2, everolimus, monocyte|
|Research Division:||Medical and Health Sciences|
|Research Field:||Immunology not elsewhere classified|
|Objective Group:||Clinical Health (Organs, Diseases and Abnormal Conditions)|
|Objective Field:||Infectious Diseases|
|Author:||Korner, H (Professor Heinrich Korner)|
|Web of Science® Times Cited:||23|
|Deposited By:||Menzies Institute for Medical Research|
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