| Urokinase receptor surface expression regulates monocyte migration and is associated with accelerated atherosclerosis. | |
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MedLine Citation:
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PMID: 22236514 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BACKGROUND: The urokinase receptor (uPAR) is a key regulator of pericellular proteolysis, cell adhesion and migration, all of which are fundamental processes in atherogenesis. We hypothesized that increased monocytic uPAR expression in circulation is associated with the formation and development of atherosclerosis. METHODS: A total of 42 male apoE-/- mice were ramdonly divided into high-fat (HF) diet and normal diet (n=21 per group). The percentage of uPAR expressing monocytes (PUEM) and the expression of uPAR within different types of atherosclerotic plaques were measured at an interval of 3weeks from week 10 to week 16. In vitro, uPAR expression upon ox-LDL stimulation and the migration of monocytes were examined. RESULTS: PUEM in circulation was significantly higher in animals with HF diet compared with those having normal diet (p<0.03). The augmented levels of PUEM were associated with body weight, visceral fat weight and numbers of uPAR+macrophages within atherosclerotic lesions. Accumulation of uPAR+macrophages increased with the progression of atherosclerosis. Monocytes upon ox-LDL stimulation exhibited an increased uPAR expression and uPAR antibody markedly suppressed monocyte migration induced by monocyte chemotactic protein-1. uPAR modulated monocyte migration was accelerated by uPA and was suppressed by amino terminal fragment of uPA dependent. CONCLUSIONS: Over-expression of uPAR both in circulating monocytes and in atherosclerotic lesions is associated with the development of atherosclerotic plaques. uPAR and its interaction with uPA may contribute to enhanced monocyte migration. Thus, uPAR may be a novel target for prevention of uncontrolled monocyte recruitment in inflammatory atherogenic process. |
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Authors:
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Wei Chen; Wei-Quan Jin; Lian-Feng Chen; Taiya Williams; Wen-Ling Zhu; Quan Fang |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-9 |
Journal Detail:
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Title: International journal of cardiology Volume: - ISSN: 1874-1754 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-12 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8200291 Medline TA: Int J Cardiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
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Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China, 100730. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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