Low molecular weight fucoidan and heparin enhance the basic fibroblast growth factor-induced tube formation of endothelial cells through heparan XXXX -dependent alpha6 overexpression.

@entity1 @entity63 @entity540 @entity13222 @entity597
Basic fibroblast growth factor ( @entity540 ) activates its high-affinity receptors (FGFRs) but also acts through interaction with heparan @entity597 proteoglycans ( @entity13222 ). Exogenous polysaccharides also modulate the angiogenic activity of @entity540 . We investigated the effect and mechanism of action of a low molecular weight fucoidan derivative (LMWF) on tube formation by @entity1 endothelial cells. LMWF has a better arterial antithrombotic potential in animals than low molecular weight heparin (LMWH). After stimulation of @entity1 umbilical vein endothelial cells (HUVEC) by @entity540 and LMWF (or LMWH), we observed 1) using flow cytometry, an increase in the amount of the alpha6 integrin subunit; 2) using quantitative reverse transcription-polymerase chain reaction, an increase in alpha6 mRNA (higher with LMWF than with LMWH); and 3) using a Matrigel model, an increase in vascular tube formation (also higher with LMWF than with LMWH). A direct link between alpha6 overexpression and vascular tube formation was confirmed by use of an anti-alpha6 antibody: in its presence, there was no capillary network formation on Matrigel. Unexpectedly, an anti-FGFR blocking antibody had no effect on alpha6 over-expression, whereas stripping off the heparan @entity597 with heparitinases abolished overexpression. Overall, our data suggest that @entity540 stimulates alpha6 over-expression in HUVEC, through @entity13222 but independently from FGFR, and that LMWF (or LMWH) modulates this interaction. Expression of heparan @entity597 proteoglycan increases after @entity63 . Given its antithrombotic properties and its ability to potentiate tube formation of endothelial cells, LMWF may have to be considered for revascularization of @entity63 areas.
