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

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 t...

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Autores principales: Haddad, Oualid, Guyot, Erwan, Marinval, Nicolas, Chevalier, Fabien, Maillard, Loïc, Gadi, Latifa, Laguillier-Morizot, Christelle, Oudar, Olivier, Sutton, Angela, Charnaux, Nathalie, Hlawaty, Hanna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4663543/
https://www.ncbi.nlm.nih.gov/pubmed/26516869
http://dx.doi.org/10.3390/md13116588
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author Haddad, Oualid
Guyot, Erwan
Marinval, Nicolas
Chevalier, Fabien
Maillard, Loïc
Gadi, Latifa
Laguillier-Morizot, Christelle
Oudar, Olivier
Sutton, Angela
Charnaux, Nathalie
Hlawaty, Hanna
author_facet Haddad, Oualid
Guyot, Erwan
Marinval, Nicolas
Chevalier, Fabien
Maillard, Loïc
Gadi, Latifa
Laguillier-Morizot, Christelle
Oudar, Olivier
Sutton, Angela
Charnaux, Nathalie
Hlawaty, Hanna
author_sort Haddad, Oualid
collection PubMed
description 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.
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spelling pubmed-46635432015-12-10 Heparanase and Syndecan-4 Are Involved in Low Molecular Weight Fucoidan-Induced Angiogenesis Haddad, Oualid Guyot, Erwan Marinval, Nicolas Chevalier, Fabien Maillard, Loïc Gadi, Latifa Laguillier-Morizot, Christelle Oudar, Olivier Sutton, Angela Charnaux, Nathalie Hlawaty, Hanna Mar Drugs Article 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. MDPI 2015-10-28 /pmc/articles/PMC4663543/ /pubmed/26516869 http://dx.doi.org/10.3390/md13116588 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Haddad, Oualid
Guyot, Erwan
Marinval, Nicolas
Chevalier, Fabien
Maillard, Loïc
Gadi, Latifa
Laguillier-Morizot, Christelle
Oudar, Olivier
Sutton, Angela
Charnaux, Nathalie
Hlawaty, Hanna
Heparanase and Syndecan-4 Are Involved in Low Molecular Weight Fucoidan-Induced Angiogenesis
title Heparanase and Syndecan-4 Are Involved in Low Molecular Weight Fucoidan-Induced Angiogenesis
title_full Heparanase and Syndecan-4 Are Involved in Low Molecular Weight Fucoidan-Induced Angiogenesis
title_fullStr Heparanase and Syndecan-4 Are Involved in Low Molecular Weight Fucoidan-Induced Angiogenesis
title_full_unstemmed Heparanase and Syndecan-4 Are Involved in Low Molecular Weight Fucoidan-Induced Angiogenesis
title_short Heparanase and Syndecan-4 Are Involved in Low Molecular Weight Fucoidan-Induced Angiogenesis
title_sort heparanase and syndecan-4 are involved in low molecular weight fucoidan-induced angiogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4663543/
https://www.ncbi.nlm.nih.gov/pubmed/26516869
http://dx.doi.org/10.3390/md13116588
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