Inhibition of angiogenic pathways in rheumatoid arthritis: potential for therapeutic targeting

Best Pract Res Clin Rheumatol. 2006 Oct;20(5):941-7. doi: 10.1016/j.berh.2006.05.004.

Abstract

Angiogenesis is a significant and possibly primary event in the pathogenesis of inflammatory diseases including arthritis. Abnormalities of vascular morphology and angiogenesis have been described at the macroscopic, histological and molecular levels in the synovial membrane in rheumatoid, seronegative and degenerative arthritis. The vascular endothelium is an active organ that participates in the initiation and maintenance of the inflammatory response. Endothelial cells (EC) are activated by a variety of stimuli to express surface adhesion molecules to bind and facilitate, via an active process, the movement of white blood cells such as neutrophils, macrophages and lymphocytes into the target tissue. The main stimuli known to activate EC and initiate angiogenesis include hypoxia, inflammatory mediators and mechanical stress. Irrespective of the trigger a series of messages, such as cytokine release, production of growth factors and subsequent downstream molecular messages, result in changes to vessel permeability, EC proliferation and migration, disruption of the basement membrane and formation of new vascular tubes. Several key growth factors are known to upregulate EC activation and proliferation leading to the sprouting of new vessels that then stabilise and mature, recruiting smooth muscle pericytes to consolidate vessel wall structure. In this review the process of angiogenesis in the arthritic joint, including the stimuli and molecular pathways will be discussed and potential therapeutic targeting of critical steps will be highlighted.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use
  • Angiostatins / therapeutic use
  • Apoptosis / physiology
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / physiopathology*
  • Cell Proliferation
  • Endothelium, Vascular / physiopathology
  • Humans
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / physiopathology*
  • Neovascularization, Pathologic / prevention & control*
  • Receptor, TIE-2 / drug effects
  • Receptor, TIE-2 / physiology
  • Tumor Necrosis Factor-alpha / physiology
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Angiogenesis Inhibitors
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • Angiostatins
  • Receptor, TIE-2