Inhibition of neovascularization in vivo by gold compounds

Abstract

As mononuclear cell infiltration and growth of pannus critically depend on synovial neovascularization in rheumatoid arthritis (RA), inhibition of the synovial blood vessels would have the potential to reduce rheumatoid inflammation. In this investigation, we studied the effect of gold sodium thiomalate (GST) and auranofin (AUR) on neovascularization in vivo by using a micropocket technique. Both GST and AUR suppressed rabbit corneal neovascularization in a dose-dependent fashion. Significant inhibition was observed by 3 mg/kg GST and 1 mg/kg AUR injected intravenously every other day. These injections maintained serum gold concentrations at the level of 2-5 micrograms/ml and less than 2 micrograms/ml in GST- and AUR-injected rabbits, respectively. These are concentrations attained in the serum or synovium of rheumatoid patients treated by gold compounds. Similar inhibition was observed by both intramuscular administration of GST and oral administration of AUR. In contrast, no inhibition was observed when non-steroidal anti-inflammatory drugs (NSAIDs; 20 mg/kg acetylsalicylic acid, 10 mg/kg ibuprofen and 10 mg/kg indomethacin) were injected intravenously on a daily basis. These results suggested that gold compounds have an antiangiogenic effect in vivo. The inhibition of neovascularization by gold compounds suggested that they may suppress rheumatoid synovitis by reducing the number of small blood vessels required for mononuclear cell infiltration and synovial tissue proliferation.

Effect of basic fibroblast growth factor on the healing of defects in the canine anterior cruciate ligament

“…As to the duration of the release of bFGF from the pellet, it seems unlikely that biological activity was maintained for more than 3 weeks in an intra-articular milieu [1,25]. Furthermore, enhancement of the healing process afforded by bFGF in this study was demonstrated mainly in the initial stage of healing.…”

“…It has already been shown that the release of several proteins from this pellet was maintained for about 6 weeks in a culture medium environment [16]. Additionally, in a study using the in vivo corneal micropocket technique [1,25], angiogenesis of the corneal microvasculature was found to continue for about 3 weeks with the use of these bFGF-impregnated pellets. Since the pellets which contained less than 1 µg bFGF had a minimal effect in a pilot study of the same experimental model, it was decided that 10 µg bFGF would be added to each pellet.…”

The biological activity of auranofin: implications for novel treatment of diseases

“…AF has been shown to directly inhibit neovascularization, which would result in decreased blood supply to neoplasms (Saura et al 1994). A molecular basis for this activity could be inhibition of TLR-3 activation and signalling ).…”