New insights in synovial angiogenesis

Abstract

Angiogenesis is the formation of new capillaries from pre-existing vessels. A number of soluble and cell-bound factors may stimulate neovascularization. The perpetuation of angiogenesis involving numerous soluble and cell surface-bound mediators has been associated with rheumatoid arthritis (RA). These angiogenic mediators, among others, include growth factors, primarily vascular endothelial growth factor (VEGF) and hypoxia-inducible factors (HIFs), as well as pro-inflammatory cytokines, various chemokines, cell adhesion molecules, proteases and others. Among the several potential angiogenesis inhibitors, targeting of VEGF, HIF-1, angiopoietin and the α V β 3 integrin, as well as some endogenous or synthetic compounds including angiostatin, endostatin, paclitaxel, fumagillin analogues, 2-methoxyestradiol and thalidomide seems to be promising for the management of synovial inflammation and angiogenesis. A complete review of antiangiogenic drugs used in animal models of arthritis or human RA is available in a table.

Peptide-siRNA nanocomplexes targeting NF-κB subunit p65 suppress nascent experimental arthritis

“…Although the etiology of RA remains controversial, the hallmark of the disease is characterized by inflammation of the synovial lining of diarthrodial joints, massive synovial proliferation, and an influx of inflammatory cells, macrophages, and lymphocytes through leaky angiogenic blood vessels (2)(3)(4). This cellular influx and synovial proliferation lead to the release of inflammatory cytokines and matrix-degrading enzymes, all of which contribute to the destruction of connective tissue, cartilage, and subchondral bone of the affected joints.…”

PGK1, a glucose metabolism enzyme, may play an important role in rheumatoid arthritis

“…In addition, Wang et al found that PGK1 participated in angiogenesis by functioning to reduce disulfide bonds in the serine protease, plasmin, which leads to the release of the tumor blood vessel inhibitor angiostatin [26]. Angiostatin is important for the management of synovial inflammation and angiogenesis [27].…”

Role of placenta growth factor in cancer and inflammation

“…Angiogenesis is finely tuned by balances between pro-angiogenic and anti-angiogenic mediators such as growth factors, cytokines, chemokines, cellular adhesion molecules and others (Szekanecz et al, 2010). Of these, VEGF and its receptors are key regulators of the angiogenic process also in inflammatory synovium of RA.…”