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  • Review Article
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Targeting of proangiogenic signalling pathways in chronic inflammation

Nature Reviews Rheumatology volume 12, pages 111–122 (2016)Cite this article

Subjects

Key Points

  • In chronic inflammatory diseases, angiogenesis enables increased delivery of oxygen and nutrients to immune cell populations accumulating in inflamed tissues, and contributes to further immune cell infiltration

  • Angiogenesis is driven not only by hypoxia, but also by proinflammatory mediators produced by immune and stromal cells

  • Many intracellular signalling pathways downstream of these proinflammatory stimuli contribute to various cellular processes involved in angiogenesis

  • Targeting these signal transduction pathways to inhibit neovascularization has been successfully exploited in several cancers, and might also prove beneficial in the treatment of chronic inflammatory diseases

Abstract

Angiogenesis is de novo capillary outgrowth from pre-existing blood vessels. This process not only is crucial for normal development, but also has an important role in supplying oxygen and nutrients to inflamed tissues, as well as in facilitating the migration of inflammatory cells to the synovium in rheumatoid arthritis, spondyloarthritis and other systemic autoimmune diseases. Neovascularization is dependent on the balance of proangiogenic and antiangiogenic mediators, including growth factors, cytokines, chemokines, cell adhesion molecules and matrix metalloproteinases. This Review describes the various intracellular signalling pathways that govern these angiogenic processes and discusses potential approaches to interfere with pathological angiogenesis, and thereby ameliorate inflammatory disease, by targeting these pathways.

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Figure 1: Overview of proangiogenic processes in chronic inflammation.
Figure 2: Inflammatory signal transduction pathways involved in (pathological) angiogenesis.
Figure 3: S1P and Notch signal transduction pathways involved in angiogenesis.

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Acknowledgements

S.W.T.'s research is supported by a VENI grant and a Clinical Fellowship from the Netherlands Organization for Scientific Research (NWO/ZonMw), and grants from the Dutch Arthritis Foundation. C.X.M.'s research is supported by a research grant from the Academic Medical Center/University of Amsterdam. Z.S.'s research is supported by grant TÁMOP-4.2.2.A-11/1/KONV-2012-0031 for projects co-financed by the European Union and the European Social Fund.

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Authors and Affiliations

  1. Department of Experimental Immunology, Amsterdam Rheumatology & Immunology Centre, Academic Medical Centre and University of Amsterdam, EULAR & FOCIS (Federation of Clinical Immunology Societies) Centre of Excellence, Meibergdreef 9, F4-105, Amsterdam, 1105 AZ, Netherlands

    Sander W. Tas & Chrissta X. Maracle

  2. Department of Rheumatology, Institute of Medicine, University of Debrecen, Faculty of Medicine, Nagyerdei Str. 98, Debrecen, 4032, Hungary

    Emese Balogh & Zoltán Szekanecz

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  1. Sander W. Tas
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  2. Chrissta X. Maracle
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Contributions

S.W.T. and C.X.M. contributed equally to this article. All authors (S.W.T., C.X.M., E.B., Z.S.) researched the data for the article and wrote the manuscript. S.W.T., E.B. and Z.S. made substantial contributions to discussion of its content. S.W.T. and Z.S. also undertook review and/or editing of manuscript before submission.

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Correspondence to Sander W. Tas.

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Tas, S., Maracle, C., Balogh, E. et al. Targeting of proangiogenic signalling pathways in chronic inflammation. Nat Rev Rheumatol 12, 111–122 (2016). https://doi.org/10.1038/nrrheum.2015.164

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