Different action of heparin and fucoidan on arterial smooth muscle cell proliferation and thrombospondin and fibronectin metabolism.
Fucoidan, a sulfated fucopolysaccharide of marine algae is able to inhibit the proliferation of arterial smooth muscle cells half maximally at a concentration of 80 to 100 micrograms/ml culture medium. In comparable concentrations heparin was significantly less active than the fucopolysaccharide. Sulfation of fucoidan was found to be essential for expression of antiproliferative activity. The inhibitory effect of fucoidan is a time-dependent event with highest effectiveness during the first 6 h. Fucoidan does not influence the overall rate of synthesis of cell proteins and glycoconjugates, but led to substantial alterations in the synthesis and secretion of fibronectin and thrombospondin. Immunoprecipitation and quantitation revealed that the incorporation of [35S]methionine into fibronectin is reduced whereas thrombospondin synthesis was increased. The effect on fibronectin was not shared by heparin. Desulfation of the fucopolysaccharide abolished the observed modulation. Binding experiments with [125I]fucoidan indicate a saturable binding and a maximum of 2.8 x 10(6) bound molecules per cell. Fucoidan binding sites can be only partly displaced by heparin. The results suggest that both heparin and the structurally unrelated sulfated fucopolysaccharide act as an antiproliferative agent but differ in their modulation of cell metabolism.
Vischer
P
P
Institut für Arterioskleroseforschung an der Universität, Münster/Bundesrepublik Deutschland.
Buddecke
E
E
D000818:Animals; D001011:Aorta / Q000166:cytology; D002455:Cell Division / Q000187:drug effects*; D002462:Cell Membrane / Q000378:metabolism; D005353:Fibronectins / Q000187:drug effects / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism*; D011134:Polysaccharides / Q000494:pharmacology*; D013552:Swine; D019699:Thrombospondins
D005353:Fibronectins; D010980:Platelet Membrane Glycoproteins; D011134:Polysaccharides; D019699:Thrombospondins; D006493:Heparin; C007789:fucoidan