title: Heparanase and Syndecan-4 Are Involved in Low Molecular Weight Fucoidan-Induced Angiogenesis.
abstract: 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.
authors.affiliation: Inserm U1148, Laboratory for Vascular Translational Science, UFR SMBH, Université Paris 13, Sorbonne Paris Cité, Groupe Biothérapies et Glycoconjugués, 93000 Bobigny, France. haddad.oualid@univ-paris13.fr.
authors.forename: Oualid
authors.initials: O
authors.lastname: Haddad
authors.affiliation: Inserm U1148, Laboratory for Vascular Translational Science, UFR SMBH, Université Paris 13, Sorbonne Paris Cité, Groupe Biothérapies et Glycoconjugués, 93000 Bobigny, France. erwan.guyot@jvr.aphp.fr.|Laboratoire de Biochimie, Hôpital Jean Verdier, Assistance Publique-Hôpitaux de Paris, 93140 Bondy, France. erwan.guyot@jvr.aphp.fr.
authors.forename: Erwan
authors.initials: E
authors.lastname: Guyot
authors.affiliation: Inserm U1148, Laboratory for Vascular Translational Science, UFR SMBH, Université Paris 13, Sorbonne Paris Cité, Groupe Biothérapies et Glycoconjugués, 93000 Bobigny, France. nmarinval@yahoo.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Marinval
authors.affiliation: ERL CNRS 9215, CRRET Laboratory, Université Paris Est Créteil, 94010 Créteil, France. fabien.che@gmail.com.
authors.forename: Fabien
authors.initials: F
authors.lastname: Chevalier
authors.affiliation: Inserm U1148, Laboratory for Vascular Translational Science, UFR SMBH, Université Paris 13, Sorbonne Paris Cité, Groupe Biothérapies et Glycoconjugués, 93000 Bobigny, France. loic_maillard95@hotmail.fr.
authors.forename: Loïc
authors.initials: L
authors.lastname: Maillard
authors.affiliation: Inserm U1148, Laboratory for Vascular Translational Science, UFR SMBH, Université Paris 13, Sorbonne Paris Cité, Groupe Biothérapies et Glycoconjugués, 93000 Bobigny, France. latifa.gadi@yahoo.fr.
authors.forename: Latifa
authors.initials: L
authors.lastname: Gadi
authors.affiliation: Inserm U1148, Laboratory for Vascular Translational Science, UFR SMBH, Université Paris 13, Sorbonne Paris Cité, Groupe Biothérapies et Glycoconjugués, 93000 Bobigny, France. christelle.laguillier@jvr.aphp.fr.|Laboratoire de Biochimie, Hôpital Jean Verdier, Assistance Publique-Hôpitaux de Paris, 93140 Bondy, France. christelle.laguillier@jvr.aphp.fr.
authors.forename: Christelle
authors.initials: C
authors.lastname: Laguillier-Morizot
authors.affiliation: Inserm U1148, Laboratory for Vascular Translational Science, UFR SMBH, Université Paris 13, Sorbonne Paris Cité, Groupe Biothérapies et Glycoconjugués, 93000 Bobigny, France. olivier.oudar@univ-paris13.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Oudar
authors.affiliation: Inserm U1148, Laboratory for Vascular Translational Science, UFR SMBH, Université Paris 13, Sorbonne Paris Cité, Groupe Biothérapies et Glycoconjugués, 93000 Bobigny, France. angela.sutton@jvr.aphp.fr.|Laboratoire de Biochimie, Hôpital Jean Verdier, Assistance Publique-Hôpitaux de Paris, 93140 Bondy, France. angela.sutton@jvr.aphp.fr.
authors.forename: Angela
authors.initials: A
authors.lastname: Sutton
authors.affiliation: Inserm U1148, Laboratory for Vascular Translational Science, UFR SMBH, Université Paris 13, Sorbonne Paris Cité, Groupe Biothérapies et Glycoconjugués, 93000 Bobigny, France. nathalie.charnaux@jvr.aphp.fr.|Laboratoire de Biochimie, Hôpital Jean Verdier, Assistance Publique-Hôpitaux de Paris, 93140 Bondy, France. nathalie.charnaux@jvr.aphp.fr.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Charnaux
authors.affiliation: Inserm U1148, Laboratory for Vascular Translational Science, UFR SMBH, Université Paris 13, Sorbonne Paris Cité, Groupe Biothérapies et Glycoconjugués, 93000 Bobigny, France. hanna.hlawaty@univ-paris13.fr.
authors.forename: Hanna
authors.initials: H
authors.lastname: Hlawaty
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D005786:Gene Expression Regulation / Q000235:genetics; D020868:Gene Silencing; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D008970:Molecular Weight; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D053668:Syndecan-1 / Q000378:metabolism; D053671:Syndecan-4 / Q000378:metabolism*; D014162:Transfection; D000099065:Exostosin 2; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D017351:N-Acetylglucosaminyltransferases; D011134:Polysaccharides; D034741:RNA, Small Interfering; D053668:Syndecan-1; D053671:Syndecan-4; D000099065:Exostosin 2; D000099175:Heparanase; C007789:fucoidan
keywords: angiogenesis; fucoidan; glycosaminoglycan; heparanase; human endothelial cell; syndecan