Role of CX3CR1 Receptor in Monocyte/Macrophage Driven Neovascularization

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Title: Role of CX3CR1 Receptor in Monocyte/Macrophage Driven Neovascularization
Authors: Kumar, Arun H.S.
Martin, Kenneth
Turner, Elizebeth C.
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Date: 21-Feb-2013
Online since: 2019-05-01T11:49:53Z
Abstract: Monocyte/Macrophages are implicated in initiation of angiogenesis, tissue/organ perfusion and atherosclerosis biology. We recently showed that chemokine receptor CX3CR1 is an essential regulator of monocyte/macrophage derived smooth muscle cell differentiation in the vessel wall after injury. Here we hypothesised the contribution of CX3CR1- CX3CL1 interaction to in vivo neovascularization and studied the functional consequences of genetic and pharmacologic targeting of CX3CR1 in formation, maturation and maintenance of microvascular integrity. Cells functionally deficient in CX3CR1 lacked matrix tunnelling and tubulation capacity in a 3D Matrigel assay. These morphogenic and cytokinetic responses were driven by CX3CL1-CX3CR1 interaction and totally abrogated by a Rho antagonist. To evaluate the role of CX3CR1 system in vivo, Matrigel plugs were implanted in competent CX3CR1+/gfp and functionally deficient CX3CR1gfp/gfp mice. Leaky microvessels (MV) were formed in the Matrigel implanted in CX3CR1gfp/gfp but not in CX3CR1+/gfp mice. In experimental plaque neovascularization immature MV phenotype was observed in CX3CR1gfp/gfp mice, lacking CX3CR1 positive smooth muscle-like cells, extracellular collagen and basement membrane (BM) laminin compared to competent CX3CR1+/gfp mice. This was associated with increased extravasation of platelets into the intima of CX3CR1gfp/gfp but not functionally competent CX3CR1 mice. Pharmacologic targeting using CX3CR1 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 CX3CR1 in Matrigel and experimental plaque neovascularization in vivo, which may buttress MV collectively in favour of a more stable non-leaky phenotype.
Funding Details: Science Foundation Ireland
Type of material: Journal Article
Publisher: PLoS
Journal: PLoS ONE
Volume: 8
Issue: 2
Start page: e57230
Copyright (published version): 2013 the Authors
Keywords: AngiogenesisChemokine receptor CX3CR1MicrovascularMacrophagesMonocyteExtravasation of plateletsNeovascularizationSingle molecule therapeutic approaches
DOI: 10.1371/journal.pone.0057230
Language: en
Status of Item: Peer reviewed
Appears in Collections:Veterinary Medicine Research Collection

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