Biochemical and Biophysical Research Communications 1996-07-16

Antiproliferative role of 3-O-sulfate glucosamine in heparin on cultured pulmonary artery smooth muscle cells.

H G Garg, P A Joseph, K Yoshida, B T Thompson, C A Hales

Index: Biochem. Biophys. Res. Commun. 224(2) , 468-73, (1996)

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Abstract

Heparin macromolecules inhibit vascular remodeling associated with hypoxic pulmonary hypertension. Heparin's antiproliferative effect on smooth muscle cells, based on studies of synthetic pentasaccharide fragments, has been attributed to 3-O-sulfate on the internal glucosamine. To 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 glucosamine residue to delta-tetrasaccharides only. Our most antiproliferative heparin gave the least amount of delta-tetrasaccharides. This heparin 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 sulfation. These studies suggest that 3-O-sulfate of glucosamine residue is not critical in whole heparins for antiproliferative activity.