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Open AccessArticle

Heparanase and Syndecan-4 Are Involved in Low Molecular Weight Fucoidan-Induced Angiogenesis

1
Inserm U1148, Laboratory for Vascular Translational Science, UFR SMBH, Université Paris 13, Sorbonne Paris Cité, Groupe Biothérapies et Glycoconjugués, 93000 Bobigny, France
2
Laboratoire de Biochimie, Hôpital Jean Verdier, Assistance Publique-Hôpitaux de Paris, 93140 Bondy, France
3
ERL CNRS 9215, CRRET Laboratory, Université Paris Est Créteil, 94010 Créteil, France
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Paola Laurienzo
Mar. Drugs 2015, 13(11), 6588-6608; https://doi.org/10.3390/md13116588
Received: 29 July 2015 / Revised: 18 September 2015 / Accepted: 19 October 2015 / Published: 28 October 2015
(This article belongs to the Collection Marine Polysaccharides)
Induction of angiogenesis is a potential treatment for chronic ischemia. Low molecular weight fucoidan (LMWF), the sulfated polysaccharide from brown seaweeds, has been shown to promote revascularization in a rat limb ischemia, increasing angiogenesis in vivo. We investigated the potential role of two heparan sulfate (HS) metabolism enzymes, exostosin-2 (EXT2) and heparanase (HPSE), and of two HS-membrane proteoglycans, syndecan-1 and -4 (SDC-1 and SDC-4), in LMWF induced angiogenesis. Our results showed that LMWF increases human vascular endothelial cell (HUVEC) migration and angiogenesis in vitro. We report that the expression and activity of the HS-degrading HPSE was increased after LMWF treatment. The phenotypic tests of LMWF-treated and EXT2- or HPSE-siRNA-transfected cells indicated that EXT2 or HPSE expression significantly affect the proangiogenic potential of LMWF. In addition, LMWF increased SDC-1, but decreased SDC-4 expressions. The effect of LMWF depends on SDC-4 expression. Silencing EXT2 or HPSE leads to an increased expression of SDC-4, providing the evidence that EXT2 and HPSE regulate the SDC-4 expression. Altogether, these data indicate that EXT2, HPSE, and SDC-4 are involved in the proangiogenic effects of LMWF, suggesting that the HS metabolism changes linked to LMWF-induced angiogenesis offer the opportunity for new therapeutic strategies of ischemic diseases. View Full-Text
Keywords: fucoidan; angiogenesis; human endothelial cell; glycosaminoglycan; syndecan; heparanase fucoidan; angiogenesis; human endothelial cell; glycosaminoglycan; syndecan; heparanase
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Haddad, O.; Guyot, E.; Marinval, N.; Chevalier, F.; Maillard, L.; Gadi, L.; Laguillier-Morizot, C.; Oudar, O.; Sutton, A.; Charnaux, N.; Hlawaty, H. Heparanase and Syndecan-4 Are Involved in Low Molecular Weight Fucoidan-Induced Angiogenesis. Mar. Drugs 2015, 13, 6588-6608.

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