Effect of fully sulfated glycosaminoglycans on pulmonary artery smooth muscle cell proliferation

Fully sulfated heparin and other glycosaminogly-cans, namely heparan, chond roitin, and dermatan sulfates, and hyaluronan have been prepared by using s ulfur trioxide under mild chemical conditions. All these derivatives were a ssayed for antiproliferative activity on cultured bovine pulmonary artery s mooth muscle cells (BPASMCs). No appreciable difference was found between h eparin and fully sulfated heparin, Chondroitin and dermatan sulfates actual ly stimulated BPASMCs growth but full sulfonation made them strongly antipr oliferative. Native hyaluronan was not antiproliferative but became strongl y so after sulfonation. Neither acharan sulfate nor N-sulfoacharan sulfate had any antiproliferative activity. This suggests that O-sulfonation of the polysaccharide is critical for antiproliferative activity, whereas N-sulfo nation of glucosamine residues is not. (C) 1999 Academic Press.