Hebatullah Laban, Andreas Weigert, Joana Miriam Zink, Amro Elgheznawy, Christoph Schürmann, Lea Günther, Randa Abdel Malik, Sabrina Bothur, Susanne Wingert, Rolf Bremer, Michael A. Rieger, Bernhard Brüne, Ralf Brandes, Ingrid Fleming, Peter M. Benz
- In ischemic vascular diseases, leukocyte recruitment and polarization are crucial for revascularization and tissue repair. We investigated the role of vasodilator-stimulated phosphoprotein (VASP) in vascular repair. After hindlimb ischemia induction, blood flow recovery, angiogenesis, arteriogenesis, and leukocyte infiltration into ischemic muscles in VASP−/− mice were accelerated. VASP deficiency also elevated the polarization of the macrophages through increased signal transducer and activator of transcription (STAT) signaling, which augmented the release of chemokines, cytokines, and growth factors to promote leukocyte recruitment and vascular repair. Importantly, VASP deletion in bone marrow–derived cells was sufficient to mimic the increased blood flow recovery of global VASP−/− mice. In chemotaxis experiments, VASP−/− neutrophils/monocytes were significantly more responsive to M1-related chemokines than wild-type controls. Mechanistically, VASP formed complexes with the chemokine receptor CCR2 and β-arrestin-2, and CCR2 receptor internalization was significantly reduced in VASP−/− leukocytes. Our data indicate that VASP is a major regulator of leukocyte recruitment and polarization in postischemic revascularization and support a novel role of VASP in chemokine receptor trafficking.
MetadatenAuthor: | Hebatullah Laban, Andreas WeigertORCiDGND, Joana Miriam ZinkGND, Amro Elgheznawy, Christoph SchürmannORCiDGND, Lea Günther, Randa Abdel Malik, Sabrina Bothur, Susanne WingertGND, Rolf Bremer, Michael A. RiegerORCiDGND, Bernhard BrüneORCiD, Ralf BrandesORCiDGND, Ingrid FlemingORCiDGND, Peter M. BenzORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-500494 |
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DOI: | https://doi.org/10.1083/jcb.201702048 |
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ISSN: | 1540-8140 |
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ISSN: | 0021-9525 |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/29507126 |
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Parent Title (English): | The journal of cell biology |
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Publisher: | Rockefeller Univ. Press |
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Place of publication: | New York, NY |
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Document Type: | Article |
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Language: | English |
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Year of Completion: | 2018 |
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Date of first Publication: | 2018/03/05 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2019/04/23 |
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Tag: | Cytoskeleton; Immunology; Physiology |
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Volume: | 217 |
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Issue: | 4 |
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Page Number: | 17 |
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First Page: | 1503 |
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Last Page: | 1519 |
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Note: | This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
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HeBIS-PPN: | 451016327 |
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Institutes: | Medizin / Medizin |
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| Wissenschaftliche Zentren und koordinierte Programme / Sonderforschungsbereiche / Forschungskollegs |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung-Keine kommerzielle Nutzung-Weitergabe unter gleichen Bedingungen |
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