| Sphingosine-1-Phosphate Receptor 3 Promotes Neointimal Hyperplasia in Mouse Iliac-Femoral Arteries. | |
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MedLine Citation:
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PMID: 22308044 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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OBJECTIVE: The objective of this study was to define a role for sphingosine-1-phosphate receptor 3 (S1PR3) in intimal hyperplasia. METHODS AND RESULTS: A denudation model of the iliac-femoral artery in wild-type and S1PR3-null mice was used to define a role for S1PR3 in the arterial injury response because we found in humans and mice that expression of S1PR3 was higher in these arteries compared with carotid arteries. At 28 days after surgery, wild-type arteries formed significantly larger lesions than S1PR3-null arteries.T Bromodeoxyuridine labeling experiments demonstrated that on injury, wild-type arteries exhibited higher medial as well as intimal proliferation than S1PR3-null arteries. Because S1PR3 expression in vitro was low, we expressed S1PR3 in S1PR3-null smooth muscle cells (SMCs) using retroviral-mediated gene transfer to study the effects of S1PR3 on cell functions and signaling. SMCs expressing S1PR3, but not vector-transfected controls, responded to sphingosine-1-phosphate stimulation with activation of Rac, Erk, and Akt. SMCs expressing S1PR3 also migrated more. CONCLUSIONS: In humans and mice, S1PR3 expression was higher in iliac-femoral arteries compared with carotid arteries. S1PR3 promoted neointimal hyperplasia on denudation of iliac-femoral arteries in mice, likely by stimulating cell migration and proliferation through activation of signaling pathways involving Erk, Akt, and Rac. |
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Authors:
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Takuya Shimizu; Allison De Wispelaere; Martin Winkler; Travis D'Souza; Jacob Caylor; Lihua Chen; Frank Dastvan; Jessie Deou; Aesim Cho; Axel Larena-Avellaneda; Michael Reidy; Guenter Daum |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-2-2 |
Journal Detail:
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Title: Arteriosclerosis, thrombosis, and vascular biology Volume: - ISSN: 1524-4636 ISO Abbreviation: - Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-2-6 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Departments of Pathology and Surgery and Center for Cardiovascular Biology, University of Washington, Seattle, WA; Department of Vascular Medicine, University Heart Center, University of Hamburg, University Hospital Hamburg-Eppendorf, Hamburg, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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