Influence of heparin chemical modifications on its antiproliferative properties

This chapter focuses on the mechanisms contributing to heparin inhibition of smooth muscle cell growth. Chronic pulmonary hypertension is characterized by structural changes in the pulmonary vasculature, which along with variable degrees of vasoconstriction, are responsible for the high pulmonary vascular resistance and associated right heart failure. Circulating HP binds to endothelial cells and is taken up by the reticuloendothelial system where it enters a cellular pool to be released at a later stage. Fully sulfated HP and other glycosaminoglycan (GAGS) are prepared by treating tributylammonium salt of these with sulfur trioxide. Sulfo groups in HP appear to play an important role in the growth inhibitory effect on smooth muscle cell proliferation. Removal of N-sulfo groups from HP reportedly negates its growth inhibitory effect on smooth muscle cells (SMCs). No appreciable difference was found between heparin and fully sulfated heparin on the growth of pulmonary artery smooth muscle cells. Chondroitin and dermatan sulfates stimulated the pulmonary artery SMCs. Hyaluronan was not antiproliferative but full sulfation made HA strongly antiproliferative against pulmonary SMCs. © 2005