Angiogenesis as a potential treatment strategy for rheumatoid arthritis

Eur J Pharmacol. 2021 Nov 5:910:174500. doi: 10.1016/j.ejphar.2021.174500. Epub 2021 Sep 9.


Angiogenesis is an early and key event in the pathogenesis of rheumatoid arthritis (RA) and is crucial for the proliferation of synovial tissue and the formation of pannus. This process is regulated by both angiogenesis-stimulating factors and angiogenesis inhibitors, the basis for the "on-off hypothesis of angiogenesis." In RA, inflammation, immune imbalance, and hypoxia can further turn on the switch for blood vessel formation and induce angiogenesis. The new vasculature can recruit white blood cells, induce immune imbalance, and aggravate inflammation. At the same time, it also can provide oxygen and nutrients for the proliferating synovial tissue, which can accelerate the process of RA. The current therapies for RA mainly target the inflammatory response of autoimmune activation. Although these therapies have been greatly improved, there are still many patients whose RA is difficult to treat or who do not fully respond to treatment. Therefore, new innovative therapies are still urgently needed. This review covers the mechanism of synovial angiogenesis in RA, including the detailed process of angiogenesis and the relationship between inflammation, immune imbalance, hypoxia, and synovial angiogenesis, respectively. At the same time, in the context of the development of angiogenesis inhibition therapy for cancer, we also discuss similar treatment strategies for RA, especially the combination of targeted angiogenesis inhibition therapy and immunotherapy.

Keywords: Angiogenesis; Angiogenesis mechanism; Angiogenic inhibitors; Angiogenic mediators; Rheumatoid arthritis.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Arthritis, Experimental / drug therapy
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / pathology
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / pathology
  • Cell Hypoxia / immunology
  • Drug Therapy, Combination / methods
  • Humans
  • Immunologic Factors / pharmacology*
  • Immunologic Factors / therapeutic use
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / immunology
  • Neovascularization, Pathologic / pathology
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Synovial Membrane / blood supply
  • Synovial Membrane / drug effects*
  • Synovial Membrane / immunology
  • Synovial Membrane / pathology


  • Angiogenesis Inhibitors
  • Immunologic Factors