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Title
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Everolimus depletes plaque macrophages, abolishes intraplaque neovascularization and improves survival in mice with advanced atherosclerosis
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Author
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Abstract
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| Background and aims Inhibition of the mechanistic target of rapamycin (mTOR) is a promising approach to halt atherogenesis in different animal models. This study evaluated whether the mTOR inhibitor everolimus can stabilize pre-existing plaques, prevent cardiovascular complications and improve survival in a mouse model of advanced atherosclerosis. Methods ApoE−/-Fbn1C1039G+/− mice (n = 24) were fed a Western diet (WD) for 12 weeks. Subsequently, mice were treated with everolimus (1.5 mg/kg daily) or vehicle for another 12 weeks while the WD continued. Results Despite hypercholesterolemia, everolimus treatment was associated with a reduction in circulating Ly6Chigh monocytes (15 vs. 28% of total leukocytes, p = 0.046), a depletion of plaque macrophages (2.1 vs. 4.1%, p = 0.040) and an abolishment of intraplaque neovascularization, which are all indicative of a more stable plaque phenotype. Moreover, everolimus reduced hypoxic brain damage and improved cardiac function, which led to increased survival (100 vs. 67% of animals, p = 0.038). Conclusions Everolimus enhances features of plaque stability and counters cardiovascular complications in ApoE−/-Fbn1C1039G+/− mice, even when administered at a later stage of the disease. |
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Language
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English
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Source (journal)
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Vascular pharmacology. - New York, N.Y.
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Publication
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New York, N.Y.
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2019
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ISSN
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1537-1891
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DOI
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10.1016/J.VPH.2018.12.004
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Volume/pages
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113
(2019)
, p. 70-76
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ISI
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000462806800008
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Pubmed ID
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30590134
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Full text (Publisher's DOI)
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Full text (open access)
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Full text (publisher's version - intranet only)
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