The Ets 1 transcription factor is upregulated during inflammatory angiogenesis in rheumatoid arthritis

Abstract

Neovascularization of the inflamed synovium and pannus is one of the hallmarks of chronic rheumatoid arthritis. It contributes to disease progression by supplying blood to the inflamed tissues and by recruiting immune competent and inflammatory cells. Angiogenesis is tightly regulated at several levels, but of significant importance is transcription. The Ets 1 transcription factor has been intimately linked to the regulation of angiogenesis under both physiological and pathological conditions and is induced in endothelial cells by vascular endothelial growth factor, the most important angiogenic factor in rheumatoid arthritis. We investigated Ets 1 expression in synovial membranes of joints in patients with active rheumatoid arthritis and compared the results to those obtained in patients with degenerative joint disease, which is characterized by significantly less neoangiogenesis. Using quantitative densitometric and real-time RT-PCR approaches, we found a significant upregulation of Ets 1 transcripts in rheumatic, compared to osteoarthritic, synovial membranes. Moreover, we were able to attribute both Ets 1 mRNA and Ets 1 protein to capillary endothelial cells of newly formed blood vessels by in situ hybridization and immunohistochemistry. Finally, our data suggest important roles of the Ets 1 transcription factor in the regulation of inflammatory angiogenesis in rheumatoid arthritis.