Alginate oligosaccharides stimulate VEGF-mediated growth and migration of human endothelial cells
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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 μg/ml in culture broth) stimulated endothelial cell growth, [3H]thymidine uptake and migration in the presence of recombinant vascular endothelial growth factor 165 (VEGF165). In contrast, a high concentration mixture of the oligosaccharides (∼100 μg/ml) suppressed cell growth. The stimulatory activity was comparable to that of heparin, with affinity to VEGF165, and decreased on heparin-induced stimulation. Each effective oligosaccharide had guluronic acid at the reducing end. A mixture of alginate oligosaccharides (5 μg/ml) and the most ¶effective fraction (1 μg/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 VEGF165-dependent stimulation of endothelial cells.
Key words Alginate oligosaccharide Endothelial cell Proliferation Migration Vascular endothelial growth factor
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© Springer-Verlag Berlin Heidelberg 1999