title: Low-sulphated oligosaccharides derived from heparan sulphate inhibit normal angiogenesis.
abstract: Heparin, with or without the addition of an adrenocorticosteroid, can inhibit normal angiogenesis in the chick embryo chorioallantoic membrane. Low- or non-sulphated heparin fragments also have anti-angiogenic effect. Attempts to define a saccharide structure responsible for the anti-angiogenic effect implicated a -[GlcA beta 1,4-GlcNAc alpha 1,4]n-sequence. This structure represents the product of the initial polymerization reaction in heparin/heparan sulphate biosynthesis. It persists in the non-sulphated regions of heparan sulphate and also occurs in the Escherichia coli K5 capsular polysaccharide. The K5 polysaccharide, fragments thereof down to octasaccharide size and analogous N-acetylated fragments of heparan sulphate, all showed anti-angiogenic activity. Hyaluronan, however, with the isomeric -[GlcA beta 1,3-GlcNAc beta 1,4]n-structure was inactive. The anti-angiogenic activity of -[GlcA beta 1,4-GlcNAc alpha 1,4]n-containing saccharides was potentiated by the presence of L-iduronic acid and one or two O-sulphate groups in the non-reducing-terminal disaccharide unit. The anti-angiogenic effect of these non- or low-sulphated saccharides was unaffected by the addition of hydrocortisone. Endothelial cell surface-bound heparan sulphate proteoglycans may represent a pool of precursors of anti-angiogenic oligosaccharides which may be of primary importance in the regulation of angiogenesis.
authors.affiliation: Department of Ophthalmology, Akademiska Sjukhuset, Uppsala, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Hahnenberger
authors.forename: A M
authors.initials: AM
authors.lastname: Jakobson
authors.forename: A
authors.initials: A
authors.lastname: Ansari
authors.forename: T
authors.initials: T
authors.lastname: Wehler
authors.forename: C M
authors.initials: CM
authors.lastname: Svahn
authors.forename: U
authors.initials: U
authors.lastname: Lindahl
mesh_terms: D000818:Animals; D016667:Bacterial Capsules; D002240:Carbohydrate Sequence; D002642:Chick Embryo; D002850:Chromatography, Gel; D006497:Heparan Sulfate / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic; D009844:Oligosaccharides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D011135:Polysaccharides, Bacterial / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: D006497:Heparan Sulfate; D009844:Oligosaccharides; D011135:Polysaccharides, Bacterial; C050673:capsular polysaccharide K5