LOW-SULFATED OLIGOSACCHARIDES DERIVED FROM HEPARAN-SULFATE INHIBIT NORMAL ANGIOGENESIS

Citation
R. Hahnenberger et al., LOW-SULFATED OLIGOSACCHARIDES DERIVED FROM HEPARAN-SULFATE INHIBIT NORMAL ANGIOGENESIS, Glycobiology, 3(6), 1993, pp. 567-573
Citations number
34
Categorie Soggetti
Biology
Journal title
ISSN journal
09596658
Volume
3
Issue
6
Year of publication
1993
Pages
567 - 573
Database
ISI
SICI code
0959-6658(1993)3:6<567:LODFHI>2.0.ZU;2-B
Abstract
Heparin, with or without the addition of an adrenocorticosteroid, can inhibit normal angiogenesis in the chick embryo chorioallantoic membra ne. Low- or non-sulphated heparin fragments also have anti-angiogenic effect. Attempts to define a saccharide structure responsible for the antiangiogenic effect implicated a -[GlcA beta 1,4-GlcNAc alpha 1,4](n )-sequence. This structure represents the product of the initial polym erization reaction in heparin/heparan sulphate biosynthesis. It persis ts in the non-sulphated regions of heparan sulphate and also occurs in the Escherichia coli K5 capsular polysaccharide. The K5 polysaccharid e, fragments thereof down to octasaccharide size and analogous N-acety lated fragments of heparan sulphate, all showed anti-angiogenic activi ty. Hyaluronan, however, with the isomeric -[GlcA beta 1,3-GlcNAc beta 1,4](n)-structure was inactive. The antiangiogenic 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 effe ct of these non- or low-sulphated saccharides was unaffected by the ad dition of hydrocortisone. Endothelial cell surface-bound heparan sulph ate proteoglycans may represent a pool of precursors of anti-angiogeni c oligosaccharides which may be of primary importance in the regulatio n of angiogenesis.