title: Antiproliferative role of 3-O-sulfate glucosamine in heparin on cultured pulmonary artery smooth muscle cells.
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.
authors.affiliation: Department of Medicine, Pulmonary/Critical Care Unit Massachusetts General Hospital, Harvard Medical School Boston 02114, USA.
authors.forename: H G
authors.initials: HG
authors.lastname: Garg
authors.forename: P A
authors.initials: PA
authors.lastname: Joseph
authors.forename: K
authors.initials: K
authors.lastname: Yoshida
authors.forename: B T
authors.initials: BT
authors.lastname: Thompson
authors.forename: C A
authors.initials: CA
authors.lastname: Hales
mesh_terms: D000818:Animals; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002810:Chondroitinases and Chondroitin Lyases; D004187:Disaccharides / Q000737:chemistry / Q000494:pharmacology; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000032:analysis / Q000494:pharmacology; D006493:Heparin / Q000737:chemistry* / Q000494:pharmacology*; D000860:Hypoxia; D051379:Mice; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D009844:Oligosaccharides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000166:cytology* / Q000187:drug effects
chemical_list: D004187:Disaccharides; D009844:Oligosaccharides; C065632:glucosamine 3-O-sulfate; D006493:Heparin; D002810:Chondroitinases and Chondroitin Lyases; D005944:Glucosamine