HIF is upregulated in synovial macrophages of RA synovium in comparison to that of osteoarthritis (OA) [129], and its expression induces the production of VEGF and platelet endothelial derived cell growth factor (PD-ECGF) [130] relating it to the vascular proliferation observed in the synovium; HIF is also connected to the production of MMP-3. This evidence concerns the gene MMP3 and rheumatoid arthritis.