| High-mobility group box protein 1 neutralization reduces development of diet-induced atherosclerosis in apolipoprotein e-deficient mice. | |
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MedLine Citation:
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PMID: 21088249 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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OBJECTIVE: High-mobility group box protein 1 (HMGB1) is a DNA-binding protein and cytokine highly expressed in atherosclerotic lesions, but its pathophysiological role in atherosclerosis is unknown. We investigated its role in the development of atherosclerosis in ApoE-/- mice. METHODS AND RESULTS: Apolipoprotein E-deficient (ApoE-/-) mice fed a high-fat diet were administered a monoclonal anti-HMGB1 neutralizing antibody, and the effects on lesion size, immune cell accumulation, and proinflammatory mediators were assessed using Oil Red O, immunohistochemistry, and real-time polymerase chain reaction. As with human atherosclerotic lesions, lesions in ApoE-/- mice expressed HMGB1. Treatment with the neutralizing antibody attenuated atherosclerosis by 55%. Macrophage accumulation was reduced by 43%, and vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1 expression was attenuated by 48% and 72%, respectively. CD11c+ dendritic cells were reduced by 65%, and the mature (CD83+) population was reduced by 60%. Treatment also reduced CD4+ cells by nearly 50%. mRNAs in lesions encoding tumor necrosis factor-α and interleukin-1β tended to be reduced. Mechanistically, HMGB1 stimulated macrophage migration in vitro and in vivo; in vivo, it markedly augmented the accumulation of F4/80+Gr-1(Ly-6C)+ macrophages and also increased F4/80+CD11b+ macrophage numbers. CONCLUSIONS: HMGB1 exerts proatherogenic effects augmenting lesion development by stimulating macrophage migration, modulating proinflammatory mediators, and encouraging the accumulation of immune and smooth muscle cells. |
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Authors:
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Peter Kanellakis; Alex Agrotis; Tin Soe Kyaw; Christine Koulis; Ingo Ahrens; Shuji Mori; Hideo K Takahashi; Keyue Liu; Karlheinz Peter; Masahiro Nishibori; Alex Bobik |
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Publication Detail:
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Type: Journal Article Date: 2010-11-18 |
Journal Detail:
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Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 31 ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-20 Completed Date: - Revised Date: - |
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: 313-9 Citation Subset: IM |
Affiliation:
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BakerIDI Heart and Diabetes Institute, PO Box 6492 St Kilda Rd Central, Melbourne, Victoria 8008, Australia. alex.bobik@baker.edu.au. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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