| Everolimus limits aortic aneurysm in the apolipoprotein E-deficient mouse by downregulating C-C chemokine receptor 2 positive monocytes. | |
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MedLine Citation:
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PMID: 23393391 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Corey S Moran; Roby J Jose; Joseph V Moxon; Alicia Roomberg; Paul E Norman; Catherine Rush; Heinrich Körner; Jonathan Golledge |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2013-02-07 |
Journal Detail:
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Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 33 ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2013 Apr |
Date Detail:
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Created Date: 2013-03-14 Completed Date: 2013-05-02 Revised Date: 2013-05-20 |
Medline Journal Info:
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Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: United States |
Other Details:
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Languages: eng Pagination: 814-21 Citation Subset: IM |
Affiliation:
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Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, School of Medicine and Dentistry, James Cook University Townsville, QLD, Australia. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Angiotensin II Animals Aorta, Abdominal / drug effects*, enzymology, immunology, pathology Aortic Aneurysm, Abdominal / chemically induced, enzymology, genetics, immunology, pathology, prevention & control* Apolipoproteins E / deficiency*, genetics Cell Movement / drug effects Cells, Cultured Disease Models, Animal Dose-Response Relationship, Drug Flow Cytometry Infusion Pumps, Implantable Infusions, Subcutaneous Interferon-gamma / metabolism Macrophages / drug effects, enzymology, immunology Male Mice Mice, Inbred C57BL Mice, Knockout Monocytes / drug effects*, enzymology, immunology, pathology Protein Kinase Inhibitors / administration & dosage, pharmacology* Receptor, Macrophage Colony-Stimulating Factor / metabolism Receptors, CCR2 / metabolism* Sirolimus / administration & dosage, analogs & derivatives*, pharmacology TOR Serine-Threonine Kinases / antagonists & inhibitors*, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Apolipoproteins E; 0/Ccr2 protein, mouse; 0/Protein Kinase Inhibitors; 0/Receptors, CCR2; 11128-99-7/Angiotensin II; 159351-69-6/everolimus; 53123-88-9/Sirolimus; 82115-62-6/Interferon-gamma; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.1.1/mTOR protein, mouse; EC 2.7.10.1/Receptor, Macrophage Colony-Stimulating Factor |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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