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.contributor.funder	Science Foundation Ireland	en
dc.contributor.funder	Agence Nationale de la Recherche	en
dc.date.accessioned	2016-02-17T11:46:19Z
dc.date.available	2016-02-17T11:46:19Z
dc.date.issued	2013
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.description.status	Peer reviewed	en
dc.description.version	Published Version	en
dc.format.mimetype	application/pdf	en
dc.identifier.articleid	e57230
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.doi	10.1371/journal.pone.0057230
dc.identifier.issn	1932-6203
dc.identifier.issued	2	en
dc.identifier.journaltitle	PLOS ONE	en
dc.identifier.uri	https://hdl.handle.net/10468/2391
dc.identifier.volume	8	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

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

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