|Budget Amount *help
¥2,000,000 (Direct Cost : ¥2,000,000)
Fiscal Year 1995 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1994 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Angiogenesis, the process of new capillary formation, participates in numerous physiological events, both normal and pathological. A number of serious diseases are dominated by abnormal neovascularization, including solid tumor growth and metastasis, diabetic retinopaathy and rheumatoid arthritis. The potential therapeutic benefit that a naturally occuring inhibitor of angiogenesis might have in controlling diseases in which neovascularization is involved has prompted a search for angiogenesis inhibitors.
Certain tissues such as cartilage are resistant to vascular invasion. Cartilage has various and much of acidic polysaccharides, and angiogenic (stimulatory) factor, such as FGF,might be regulated by heparan sulfate. Moreover, angiogenesis begin from the triggering that an angiogenic factor activates vascular endothelial cells, therefore the suppression of trigger is important, as compared with inhibition of each step of angiogenesis. Acidic polysaccharides might be candidate for angige
nic inhibitor. We examined the inhibitory effect of various acidic polysaccharides from all kinds of marine algae, which are rich sources of them, the inhibitory behavior, the effect for FGF function and the regulatory mechanism of them, on angiogenesis.
The results obtained showed the following : (1) Fucoidan from brown algae markedly showed an inhibitory activity of angiogenesis and porphyran showed a weak activity. Among of acidic polysaccharides from five unknown monocellular algae in marine, we could find two polysaccharides which show the strong inhibition on angiogenesis ; (2) Both of porphyran and dextran sulfate markedly suppressed the migration and tube formation in vitro, even in the induced condition by FGF ; (3) Both of inhibition of angiogenesis in vivo and migration in vitro by acidic polysaccharides depend on sulfate contents ; (4) Sulfated polysaccharides enhanced the adhesion for culture plates ; (5) We succeeded to get the low molecular and active porphyran on the inhibition of angiogenesis without anti-blood coagulation function ; (6) In the structure unknownacidic polysaccharides from monocellular algae in marine which we found, it was suggested that sulfate contents is important in the exertion of anti-angiogenic function.
These data suggest that the functional point of angiogenic inhibition by acidic polysaccharides is the suppression of activation of vascular endothelial cells by angiogenic factor. Less