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 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.