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Mar. Drugs 2016, 14(10), 185;

Identification of a Pro-Angiogenic Potential and Cellular Uptake Mechanism of a LMW Highly Sulfated Fraction of Fucoidan from Ascophyllum nodosum

Inserm U1148, LVTS, Université Paris 13, Sorbonne Paris Cité, Paris 75018, France
Laboratoire CSPBAT, CNRS UMR 7244, UFR SMBH, Université Paris 13, Sorbonne Paris Cité, Bobigny F-93017, France
Laboratoire de Biochimie, Hôpital Jean Verdier, Assistance Publique-Hôpitaux de Paris, Bondy 93140, France
Author to whom correspondence should be addressed.
Academic Editor: Paola Laurienzo
Received: 28 September 2016 / Revised: 28 September 2016 / Accepted: 10 October 2016 / Published: 17 October 2016
(This article belongs to the Collection Marine Polysaccharides)
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Herein we investigate the structure/function relationships of fucoidans from Ascophyllum nodosum to analyze their pro-angiogenic effect and cellular uptake in native and glycosaminoglycan-free (GAG-free) human endothelial cells (HUVECs). Fucoidans are marine sulfated polysaccharides, which act as glycosaminoglycans mimetics. We hypothesized that the size and sulfation rate of fucoidans influence their ability to induce pro-angiogenic processes independently of GAGs. We collected two fractions of fucoidans, Low and Medium Molecular Weight Fucoidan (LMWF and MMWF, respectively) by size exclusion chromatography and characterized their composition (sulfate, fucose and uronic acid) by colorimetric measurement and Raman and FT-IR spectroscopy. The high affinities of fractionated fucoidans to heparin binding proteins were confirmed by Surface Plasmon Resonance. We evidenced that LMWF has a higher pro-angiogenic (2D-angiogenesis on Matrigel) and pro-migratory (Boyden chamber) potential on HUVECs, compared to MMWF. Interestingly, in a GAG-free HUVECs model, LMWF kept a pro-angiogenic potential. Finally, to evaluate the association of LMWF-induced biological effects and its cellular uptake, we analyzed by confocal microscopy the GAGs involvement in the internalization of a fluorescent LMWF. The fluorescent LMWF was mainly internalized through HUVEC clathrin-dependent endocytosis in which GAGs were partially involved. In conclusion, a better characterization of the relationships between the fucoidan structure and its pro-angiogenic potential in GAG-free endothelial cells was required to identify an adapted fucoidan to enhance vascular repair in ischemia. View Full-Text
Keywords: fucoidan; glycosaminoglycans; glycocalyx; angiogenesis; endocytosis fucoidan; glycosaminoglycans; glycocalyx; angiogenesis; endocytosis

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Marinval, N.; Saboural, P.; Haddad, O.; Maire, M.; Bassand, K.; Geinguenaud, F.; Djaker, N.; Ben Akrout, K.; Lamy de la Chapelle, M.; Robert, R.; Oudar, O.; Guyot, E.; Laguillier-Morizot, C.; Sutton, A.; Chauvierre, C.; Chaubet, F.; Charnaux, N.; Hlawaty, H. Identification of a Pro-Angiogenic Potential and Cellular Uptake Mechanism of a LMW Highly Sulfated Fraction of Fucoidan from Ascophyllum nodosum. Mar. Drugs 2016, 14, 185.

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