In systemic inflammatory diseases (such as RA, SLE, inflammatory bowel diseases, psoriasis, spondyloarthritis and others) multiple factors, including tumor necrosis factor-α (TNF-α), circulating inflammatory cytokines, reactive oxygen species, autoantibodies, and oxidized low density lipoprotein (LDL) directly and indirectly activate endothelial cells, increased endothelial permeability, increased leukocyte adhesion and generation of a pro-thrombotic state. Here, TNF is linked to rheumatoid arthritis.