Neovascularization is regulated by angiogenic factors such as vascular endothelial growth factor (VEGF) and angiopoietins (ANGPT1 and ANGPT2), which bind to TIE2. Interactions between rheumatoid arthritis synovial fibroblasts (RASFs) and endothelial cells promote pathogenic vascularization in the rheumatoid arthritis (RA) synovium. Understanding how RASF–endothelial cell interactions alter vascularization in RA might reveal therapeutic targets.

Heck et al. provide insights into how RASFs alter neovascularization in RA. The authors use the severe combined immunodeficient (SCID) mouse model of RA, which involves implanting healthy human cartilage and RASFs into SCID mice. In this model, RASFs induced pathogenic helix-like vessel formation in both ipsilateral (site of RASF and cartilage implantation) and contralateral (distal cartilage implantation) sites. ANGPT2 expression on endothelial cells in RA synovial tissue and in SCID mouse implants was increased compared with control samples (osteoarthritis synovial tissue and control implants, respectively). In addition, culturing an endothelial cell line with RASFs upregulated ANGPT2 compared with untreated cells.