ANTIPROLIFERATIVE ROLE OF 3-O-SULFATE GLUCOSAMINE IN HEPARIN ON CULTURED PULMONARY-ARTERY SMOOTH-MUSCLE CELLS

Heparin macromolecules inhibit vascular remodeling associated with hyp oxic pulmonary hypertension. Heparin's antiproliferative effect on smo oth muscle cells, based on studies of synthetic pentasaccharide fragme nts, has been attributed to 3-O-sulfate on the internal glucosamine. T o determine the role of 3-O-sulfation in smooth muscle cell growth, we treated three heparins of varying potency with heparitinases I and II , which degrade heparin fragments containing 3-O-sulfate on the glucos amine residue to Delta-tetrassacchharides only. Our most antiprolifera tive heparin gave the least amount of Delta-tetrasaccharides. This hep arin was then fractionated according to degree of sulfation using ETOH precipitation. Again we found no antiproliferative difference between the highly sulfated fractions and those with a lesser degree of sulfa tion. These studies suggest that 3-O-sulfate of glucosamine residue is not critical in whole heparins for antiproliferative activity. (C) 19 96 Academic Press, Inc.