Synovial fibroblasts in RA patients express an endogenous TLR ligand called high-mobility group box 1 (HMGB-1), which up-regulates expression of VEGF, thereby exacerbating RA [168], though inhibition of HIF-1α leads to attenuation of the HMGB-1 protein. This evidence concerns the gene VEGFA and rheumatoid arthritis.