Sulfated polysaccharides act as modulators of cell proliferation and expression of extracellular matrix proteins — fibronectin and thrombospondin — in arterial wall cells

Abstract

Several sulfated polysaccharides were investigated in regard to their action on cell proliferation and modulation of cellular protein metabolism in arterial wall cells. 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 µg/ml culture medium. Heparin was significantly less active than the fucopolysaccharide. The inhibitory effect of fucoidan is a time dependent event and sulfation of the polysaccharide is essential.

Fucoidan did not influence the overall rate of cell protein and glycoconjugate synthesis, but led to substantial alterations in the synthesis and secretion of fibronectin and thrombospondin. The effect on fibronectin was not shared by heparin.

Binding experiments with [¹²⁵I] fucoidan indicate a saturable binding at the cell surface of smooth muscle cells with a maximum of 2.8 × 10⁶ bound molecules per cell. Fucoidan binding sites can be only partly displaced by heparin. The results suggest that heparin and fucoidan act as antiproliferative agents but differ in their modulation of cell metabolism.

Zusammenfassung

Die Proliferation und Migration von glatten Muskelzellen aus der Media in den subendothelialen Raum ist ein zentrales Ereignis in der Frühphase der Atherogenese [6]. Unter physiologischen Bedingungen befinden sich die glatten Muskelzellen der Arterienwand im Ruhezustand, und erst unter dem Einfluß einer „funktionellen Läsion“ kommt es zu einer Reaktion auf Wachstumsfaktoren bzw. Zytokine, die aus Thrombozyten, Endothelzellen oder Makrophagen freigesetzt werden.