Focally regulated endothelial proliferation and cell death in human synovium

Am J Pathol. 1998 Mar;152(3):691-702.


Angiogenesis and vascular insufficiency each may support the chronic synovial inflammation of rheumatoid arthritis. We have shown by quantitative immunohistochemistry and terminal uridyl deoxynucleotide nick end labeling that endothelial proliferation and cell death indices were each increased in synovia from patients with rheumatoid arthritis compared with osteoarthritic and noninflamed controls, whereas endothelial fractional areas did not differ significantly among disease groups. Markers of proliferation were associated with foci immunoreactive for vascular endothelial growth factor and integrin alpha(v)beta3, whereas cell death was observed in foci in which immunoreactivities for these factors were weak or absent. No association was found with thrombospondin immunoreactivity. The balance between angiogenesis and vascular regression in rheumatoid synovitis may be determined by the focal expression of angiogenic and endothelial survival factors. Increased endothelial cell turnover may contribute to microvascular dysfunction and thereby facilitate persistent synovitis.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Apoptosis*
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / pathology*
  • Cell Division
  • Endothelial Growth Factors / metabolism
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology*
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / metabolism
  • Lymphokines / metabolism
  • Male
  • Middle Aged
  • Osteoarthritis / metabolism
  • Osteoarthritis / pathology*
  • Proliferating Cell Nuclear Antigen / metabolism
  • Rats
  • Receptors, Vitronectin / metabolism
  • Synovial Membrane / blood supply
  • Synovial Membrane / metabolism
  • Synovial Membrane / pathology*
  • Thrombospondins / metabolism
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Endothelial Growth Factors
  • Ki-67 Antigen
  • Lymphokines
  • Proliferating Cell Nuclear Antigen
  • Receptors, Vitronectin
  • Thrombospondins
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors