title: Alginate oligosaccharides stimulate VEGF-mediated growth and migration of human endothelial cells.
abstract: Alginate oligosaccharides cleaved from alginic acid polysaccharides of seaweed were tested to determine their ability to enhance proliferation and migration of human umbilical vein endothelial cells. A mixture of alginate oligosaccharides (5 microg/ml in culture broth) stimulated endothelial cell growth, [(3)H]thymidine uptake and migration in the presence of recombinant vascular endothelial growth factor 165 (VEGF(165)). In contrast, a high concentration mixture of the oligosaccharides ( approximately 100 microg/ml) suppressed cell growth. The stimulatory activity was comparable to that of heparin, with affinity to VEGF(165), and decreased on heparin-induced stimulation. Each effective oligosaccharide had guluronic acid at the reducing end. A mixture of alginate oligosaccharides (5 microg/ml) and the most paragraph signeffective fraction (1 microg/ml) stimulated endothelial cell migration. In the presence of VEGF and heparin, some alginate oligosaccharides with the peripheral guluronic acid demonstrated marked stimulatory effects, and one fraction also showed a migratory effect. These findings indicate novel activities of alginate oligosaccharide(s) in endothelial cell growth and migration and suggest synergistic and/or stabilizing effects on VEGF(165)-dependent stimulation of endothelial cells.
authors.affiliation: Department of Dermatology, Kinki University School of Medicine, 377-2, Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kawada
authors.forename: N
authors.initials: N
authors.lastname: Hiura
authors.forename: S
authors.initials: S
authors.lastname: Tajima
authors.forename: H
authors.initials: H
authors.lastname: Takahara
mesh_terms: D000464:Alginates / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004338:Drug Combinations; D016228:Endothelial Growth Factors / Q000494:pharmacology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007231:Infant, Newborn; D008222:Lymphokines / Q000494:pharmacology / Q000502:physiology*; D009844:Oligosaccharides / Q000494:pharmacology*; D009994:Osmolar Concentration; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D000464:Alginates; D004338:Drug Combinations; D016228:Endothelial Growth Factors; D008222:Lymphokines; D009844:Oligosaccharides; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D006493:Heparin