FOCALLY REGULATED ENDOTHELIAL PROLIFERATION AND CELL-DEATH IN HUMAN SYNOVIUM

Angiogenesis and vascular insufficiency each may support the chronic s ynovial inflammation of rheumatoid arthritis. We have shown by quantit ative immunohistochemistry and terminal uridyl deoxynucleotide nick en d labeling that endothelial proliferation and cell death indices were each increased in synovia from patients with rheumatoid arthritis comp ared with osteoarthritic and noninflamed controls, whereas endothelial fractional areas did not differ significantly among disease groups. M arkers of proliferation were associated with foci immunoreactive for v ascular endothelial growth factor and integrin alpha(v) beta(3), where as cell death was observed in foci in which immunoreactivities for the se factors were weak or absent. No association was found with thrombos pondin immunoreactivity. The balance between angiogenesis and vascular regression in rheumatoid synovitis may be determined by the focal exp ression of angiogenic and endothelial survival factors. Increased endo thelial cell turnover may contribute to microvascular dysfunction and thereby facilitate persistent synovitis.