Role of CX(3)CR1 receptor in monocyte/macrophage driven neovascularization

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dc.contributor.author Kumar, Arun H. S.
dc.contributor.author Martin, Kenneth
dc.contributor.author Turner, Elizebeth C.
dc.contributor.author Buneker, Chirlei K.
dc.contributor.author Dorgham, Karim
dc.contributor.author Deterre, Philippe
dc.contributor.author Caplice, Noel M.
dc.date.accessioned 2016-02-17T11:46:19Z
dc.date.available 2016-02-17T11:46:19Z
dc.date.issued 2013
dc.identifier.citation Kumar AHS, Martin K, Turner EC, Buneker CK, Dorgham K, Deterre P, et al. (2013) Role of CX3CR1 Receptor in Monocyte/Macrophage Driven Neovascularization. PLoS ONE 8(2): e57230. doi:10.1371/journal.pone.0057230 en
dc.identifier.volume 8 en
dc.identifier.issued 2 en
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/10468/2391
dc.identifier.doi 10.1371/journal.pone.0057230
dc.description.abstract Monocyte/Macrophages are implicated in initiation of angiogenesis, tissue/organ perfusion and atherosclerosis biology. We recently showed that chemokine receptor CX(3)CR1 is an essential regulator of monocyte/macrophage derived smooth muscle cell differentiation in the vessel wall after injury. Here we hypothesised the contribution of CX(3)CR1- CX(3)CL1 interaction to in vivo neovascularization and studied the functional consequences of genetic and pharmacologic targeting of CX(3)CR1 in formation, maturation and maintenance of microvascular integrity. Cells functionally deficient in CX(3)CR1 lacked matrix tunnelling and tubulation capacity in a 3D Matrigel assay. These morphogenic and cytokinetic responses were driven by CX(3)CL1-CX(3)CR1 interaction and totally abrogated by a Rho antagonist. To evaluate the role of CX(3)CR1 system in vivo, Matrigel plugs were implanted in competent CX(3)CR1(+/gfp) and functionally deficient CX(3)CR1(gfp/gfp) mice. Leaky microvessels (MV) were formed in the Matrigel implanted in CX(3)CR1(gfp/gfp) but not in CX(3)CR1(+/gfp) mice. In experimental plaque neovascularization immature MV phenotype was observed in CX(3)CR1(gfp/gfp) mice, lacking CX(3)CR1 positive smooth muscle-like cells, extracellular collagen and basement membrane (BM) laminin compared to competent CX(3)CR1(+/gfp) mice. This was associated with increased extravasation of platelets into the intima of CX(3)CR1(gfp/gfp) but not functionally competent CX(3)CR1 mice. Pharmacologic targeting using CX(3)CR1 receptor antagonist in wild type mice resulted in formation of plaque MV with poor BM coverage and a leaky phenotype. Our data indicate a hitherto unrecognised role for functional CX(3)CR1 in Matrigel and experimental plaque neovascularization in vivo, which may buttress MV collectively in favour of a more stable non-leaky phenotype. en
dc.description.sponsorship Science Foundation Ireland (SFI PI and RFP-NMC); Agence National de la Recherché, France (n°ANR-09-PIRI-0003) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Public Library of Science en
dc.rights © 2013 Kumar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited en
dc.rights.uri http://creativecommons.org/licenses/by/4.0/ en
dc.subject Muscle cell differentiation en
dc.subject Plaque rupture en
dc.subject Antiangiogenic therapy en
dc.subject Progenitor cells en
dc.subject Angiogenesis en
dc.subject Macrophages en
dc.subject Fractalkine en
dc.subject Atherosclerosis en
dc.subject Mice en
dc.subject Collagen en
dc.title Role of CX(3)CR1 receptor in monocyte/macrophage driven neovascularization en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Noel M. Caplice, Medicine, University College Cork, Cork, Ireland. +353-21-490-3000 Email: n.caplice@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.internal.wokid WOS:000315186000087
dc.contributor.funder Science Foundation Ireland en
dc.contributor.funder Agence Nationale de la Recherche en
dc.description.status Peer reviewed en
dc.identifier.journaltitle PLOS ONE en
dc.internal.IRISemailaddress n.caplice@ucc.ie en
dc.identifier.articleid e57230


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© 2013 Kumar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Except where otherwise noted, this item's license is described as © 2013 Kumar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
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