0024 : Angiogenesis potentialized by highly sulfated fucoidan: role of the chemokines and the proteoglycans

Fucoidans are natural sulfated polysaccharides used as glycosaminoglycans (GAG) mimetics. Both GAGs and chemokines are important to regulate angiogenesis and wound healing. Fucoidans interacts with pro-angiogenic chemokines, such as RANTES and SDF-1, leads to revascularization and increases endothelial cell migration. However this pro-angiogenic activity remains unclear and depends of the type of fucoidan. Innovative vascular therapies based on GAG mimetic should be developed.Upstream of developing a tissue engineering therapy, we propose to understand the beneficial effect of fucoidans on angiogenesis by a structure-function study. We hypothesize that the size and sulfation level could regulate the chemokines affinity and modulate its beneficial properties.We purified and characterized 5 fractions of fucoidans according to their sulfation rate. We tested their affinity to chemokines (Surface Plasmon Resonance), the effect on endothelial cells (HUVEC) migration (Boyden chamber) and their pro-angiogenic properties (Microvascular network formation). We also analyzed the effect of fucoidans on endogen proteoglycans and GAG expression (qRT-PCR, FACS).The structural analysis of fucoidans resulted in fractions (5-27kDa) composed of fucose, sulfate and uronic acid. The most sulfated fraction (5kDa with the ratio sulfate/fucose at 1.87) presented high affinity to biotinylated-SDF-1 and RANTES. Furthermore, this 5kDa fucoidan significantly increased HUVEC migration and microvascular network formation compared to other fractions.The 5 kDa fucoidan shows the highest pro-angiogenic effects on HUVEC. Sulfate-rich 5kDa fucoidan confirmed our hypothesis than small and highly sulfated fucoidan is attractive candidate to develop therapies based on revascularization. We now focus to develop regenerative cell therapy of ischemic heart based on the injection of progenitors cells coupled with pro-angiogenic fucoidan and chemokines