EFFECT OF THE DESULFATION OF HEPARIN ON ITS ANTICOAGULANT AND ANTIPROLIFERATIVE ACTIVITY

Some glycosaminoglycans (GAGs), such as heparin and heparin-like compo unds inhibit the proliferation of several cell types, including smooth muscle cells, cervical epithelial cells and fibroblasts (1-3). In ord er to establish which domain of the hepar-in molecule is specifically responsible for the anti-proliferative activity, several strategies ha ve been adopted such as: chemical modification or fractionation of the heparin molecule into low molecular weight fragments or synthesis of oligosaccharides with a defined chemical structure (4-6). In the prese nt study we attempted to determine the role of N- and 0- linked sulfat e groups on the anti-proliferative and anticoagulant effect of heparin . To that purpose we modified the molecule to produce N-desulfated, 0- desulfated compounds. The anti-proliferative activity of these modifie d heparins was compared to that of low molecular weight heparins obtai ned by depolymerization, heparan sulfate as N-acetylated compound with glucuronic acid and heparin. Since the anti-proliferative effect of h eparin depends also on the cell type, we used two different cell types : BHK-21 (hamster fibroblasts) and human arterial SMC (smooth muscle c ells), that were found to exhibit a high or intermediate sensitivity t o heparin (3,7).