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MCP-1 promotes mural cell recruitment during angiogenesis in the aortic ring model

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Abstract

Rings of rat or mouse aorta embedded in collagen gels produce angiogenic outgrowths in response to the injury of the dissection procedure. Aortic outgrowths are composed of branching endothelial tubes and surrounding mural cells. Mural cells emerge following endothelial sprouting and gradually increase during the maturation of the neovessels. Treatment of aortic cultures with angiopoietin-1 (Ang-1), an angiogenic factor implicated in vascular maturation and remodeling, stimulates the mural cell recruitment process. Ang-1 induces expression of many cytokines and chemokines including monocyte chemotactic protein-1 (MCP-1). Inhibition of p38 MAP kinase, a signaling molecule required for mural cell recruitment, blocks Ang1-induced MCP-1 expression. Recombinant MCP-1 dose-dependently increases mural cell number while an anti-MCP-1 blocking antibody reduces it. In addition, antibody mediated neutralization of MCP-1 abrogates the stimulatory effect of Ang-1 on mural cell recruitment. Aortic rings from genetically modified mice deficient in MCP-1 or its receptor CCR2 have fewer mural cells than controls. MCP-1 deficiency also impairs the mural cell recruitment activity of Ang-1. Our studies indicate that spontaneous and Ang1-induced mural cell recruitment in the aortic ring of model of angiogenesis are in part mediated by MCP-1. These results implicate MCP-1 as one of the mediators of mural cell recruitment in the aortic ring model, and suggest that chemokine pathways may contribute to the assembly of the vessel wall during the angiogenesis response to injury.

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Abbreviations

Ang-1:

Angiopoietin-1

bFGF:

Basic fibroblast growth factor

EBM:

Endothelial basal medium

HB-EGF:

Heparin binding-endothelial growth factor

HGF:

Hepatocyte growth factor

MCP-1:

Monocyte chemotactic protein-1

VEGF:

Vascular endothelial growth factor

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Acknowledgments

Supported by the National Institute of Health (HL52585; R.F.N.) and the Medical Research Service, Department of Veterans Affairs (R.F.N.).

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Authors and Affiliations

  1. Department of Pathology, University of Washington, Seattle, WA, USA

    Alfred C. Aplin & Roberto F. Nicosia

  2. Division of Pathology and Laboratory Medicine (S-113), Veterans Administration Puget Sound Health Care System, 1660 South Columbian Way, Seattle, WA, 98108, USA

    Eric Fogel & Roberto F. Nicosia

Authors
  1. Alfred C. Aplin
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Correspondence to Roberto F. Nicosia.

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Aplin, A.C., Fogel, E. & Nicosia, R.F. MCP-1 promotes mural cell recruitment during angiogenesis in the aortic ring model. Angiogenesis 13, 219–226 (2010). https://doi.org/10.1007/s10456-010-9179-8

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  • DOI: https://doi.org/10.1007/s10456-010-9179-8

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