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Mechanisms of Disease: angiogenesis in inflammatory diseases

Nature Clinical Practice Rheumatology volume 3, pages 635–643 (2007)Cite this article

Abstract

Angiogenesis, the development of new vessels, is an important process in health and disease. The perpetuation of neovascularization in inflammatory diseases, such as rheumatoid arthritis, spondyloarthropathies and some systemic autoimmune diseases, might facilitate the ingress of inflammatory cells into the synovium and, therefore, stimulate pannus formation. Disorders associated with perpetuated neovascularization are considered to be angiogenic inflammatory diseases. Several angiogenic mediators, including growth factors, cytokines, matrix metalloproteinases, matrix macromolecules, cell adhesion receptors, chemokines and chemokine receptors, have been implicated in the process of capillary formation. There is a regulatory network in inflamed tissues that is involved in the upregulation or downregulation of angiogenesis. Endogenous angiostatic factors downregulate neovascularization and might act as angiostatic agents. Furthermore, angiogenesis might be targeted by several specific approaches that could be therapeutically used to control inflammatory diseases.

Key Points

  • Angiogenesis, the formation of new vessels, is a key mechanism involved in leukocyte ingress through the vascular endothelium into sites of inflammation

  • Numerous inflammatory rheumatic diseases, including rheumatoid arthritis, spondyloarthropathies and systemic lupus erythematosus, can be considered to be angiogenic diseases, as they are associated with intensive angiogenesis

  • In inflammation, there is an imbalance between angiogenic and angiostatic mediators, leading to the perpetuation of neovascularization

  • Angiogenic mediators and inhibitors include cytokines, chemokines, growth factors, adhesion molecules, proteases, and synthetic compounds

  • There is a regulatory network in inflamed tissues, which is involved in the control of angiogenesis

  • Specific targeting of angiogenesis might be used as a therapeutic approach to control inflammation

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Figure 1: The angiogenic process and mediators of angiogenesis.
Figure 2: Inhibitors of angiogenesis and therapeutic targets.

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Acknowledgements

This work was supported by NIH grants (AEK), the William D Robinson, MD and Frederick GL Huetwell Endowed Professorship (AEK), funds from the Veterans' Administration (AEK); and a grant from the National Scientific Research Fund (OTKA; Z.S.). We are sorry that, due to space limitations, we were not able to include more references from key contributors in the field.

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Authors and Affiliations

  1. and Head of the Rheumatology Division at the University of Debrecen Medical Center, Z Szekanecz is Associate Professor of Medicine, Rheumatology and Immunology, Institute of Internal Medicine, Debrecen, Hungary.,

    Zoltán Szekanecz

  2. AE Koch is the Frederick GL Huetwell and William D Robinson Professor of Rheumatology at the University of Michigan Medical School, Ann Arbor, MI, USA.,

    Alisa E Koch

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  1. Zoltán Szekanecz
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Correspondence to Zoltán Szekanecz.

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Competing interests

AE Koch has acted as a Consultant for Actelion Ltd, Astra Zeneca PLC, Clinical Advisors LLC, Genentech, Inc, Gerson Lehrman Group, Incyte Corporation, Micromet, Predix Pharmaceuticals, Proctor and Gamble, and TAP pharmaceutical Products Inc. She has received research support from the NIH, Predix Pharmaceuticals, TAP pharmaceutical Products Inc. and the Veterans Administration. Z Szekanecz declared no competing interests.

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Szekanecz, Z., Koch, A. Mechanisms of Disease: angiogenesis in inflammatory diseases. Nat Rev Rheumatol 3, 635–643 (2007). https://doi.org/10.1038/ncprheum0647

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