Effect of an oversulfated exopolysaccharide on angiogenesis induced by fibroblast growth factor-2 or vascular endothelial growth factor in vitro

• Published in: Biochemical pharmacology Vol. 69; no. 5; pp. 751 - 759
• Main Authors: Matou, Sabine, Colliec-Jouault, Sylvia, Galy-Fauroux, Isabelle, Ratiskol, Jacqueline, Sinquin, Corinne, Guezennec, Jean, Fischer, Anne-Marie, Helley, Dominique
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.03.2005; Elsevier Science
• Subjects: Angiogenesis; Angiogenic growth factor; Biological and medical sciences; Cardiovascular system; Cell Differentiation - drug effects; Cell Movement - drug effects; Cell Proliferation - drug effects; Cells, Cultured; Collagen gel; Drug Synergism; Endothelial Cells - cytology; Endothelial Cells - drug effects; Fibroblast Growth Factor 2 - pharmacology; Humans; Matrigel; Medical sciences; Miscellaneous; Neovascularization, Physiologic - drug effects; Pharmacology. Drug treatments; Polysaccharide; Polysaccharides, Bacterial - pharmacology; Vascular Endothelial Growth Factors - pharmacology; α 6 Integrin subunit; HSPG; Collagen gel; VEGF; EPS; OS-EPS; FGF-2; Angiogenesis; HMW; FBS; Angiogenic growth factor; LMW; α 6 Integrin subunit; Matrigel; HUVEC; Polysaccharide; Human; Fibroblast growth factor; Endothelial cell; Glycoprotein; Subunit; In vitro; Alteromonas; Colloidal gel; Vascular endothelium growth factor; Integrin; Collagen; α6 Integrin subunit; Bacteria; Umbilical vein
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/j.bcp.2004.11.021

The aim of this study was to determine the angiogenic properties of an oversulfated exopolysaccharide (OS-EPS) derived from a polysaccharide secreted by the mesophilic bacterium Alteromonas infernus. We compared the effect of this OS-EPS with that of a non-oversulfated exopolysaccharide (EPS) on human umbilical vein endothelial cell (HUVEC) proliferation, migration and differentiation induced by basic fibroblast growth factor (FGF-2) or vascular endothelial growth factor (VEGF). OS-EPS enhanced HUVEC proliferation by 58% when used alone, and by respectively 30% and 70% in the presence of FGF-2 and VEGF. OS-EPS also increased the density of tubular structures on Matrigel in the presence of FGF-2 or VEGF. Vascular tube formation was related to α 6 integrin subunit expression, which was enhanced by 50% in the presence of the growth factors. Indeed, a monoclonal anti-α 6 blocking antibody abolished this vascular tube formation. EPS had no effect in any of the experimental conditions, underlying the importance of sulfation in the angiogenic effects of exopolysaccharide. By potentiating the angiogenic activity of FGF-2 and/or VEGF, OS-EPS, which possesses low anticoagulant activity and thus a low hemorrhagic risk, could potentially be used to accelerate vascular wound healing or to promote the growth of collateral blood vessels in ischemic tissues.