Activity of pentosan polysulphate and derived compounds on vascular endothelial cell proliferation and migration induced by acidic and basic FGF in vitro.
Pentosan polysulphate (PPS, SP 54, HEMOCLAR), a highly sulphated semi-synthetic polysaccharide of MW 4700 Daltons is as efficient as heparin in potentiating the mitogenic activity of acidic FGF (aFGF) on human umbilical vein endothelial cells (HUVEC). When added to basic FGF (bFGF), no effect was observed on these cells. However, PPS had a strong inhibitory effect on the growth of bovine aortic endothelial cells (BAEC), as did heparin. PPS was fractionated according to molecular weight and the activities of these fractions were compared. A PPS fraction of MW = 3200 Daltons represented the critical size required to affect cell proliferation induced by FGFs. We also report that acidic and basic FGFs are both chemotactic for BAEC and HUVEC. PPS and heparin, which were chemotactic alone on BAEC, potentiated acidic FGF-induced migration but inhibited the chemotactic response of basic FGF. These data suggest that PPS, although having a different structure, can mimic the in vitro activity of heparin on FGF-induced proliferation and migration of endothelial cells and thus the possibility of a specific heparin sequence being involved in the interactions with FGFs can be questioned.
Herbert
J M
JM
Sanofi Recherche, Toulouse, France.
Cottineau
M
M
Driot
F
F
Pereillo
J M
JM
Maffrand
J P
JP
D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects*; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008970:Molecular Weight; D010426:Pentosan Sulfuric Polyester / Q000494:pharmacology*; D011134:Polysaccharides / Q000494:pharmacology*
D011134:Polysaccharides; D010426:Pentosan Sulfuric Polyester; D005346:Fibroblast Growth Factors; D006493:Heparin