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. Cependant, il existe d'autres hypothèses qui proposent que les fucoïdanes, ayant la capacité de se lier au HBPs, pourraient également entrer en compétition avec les HBPs et à l'inhibition des leurs effets. Ceci suggère que l'activité pro-angiogénique du LMWF n'est pas liée à sa capacité à se lier aux HBPs, 2007.

, A l'inverse, le fucoïdane pourrait en absence de l'expression des GAGs dans un modèle de l'hyperplasie intimale, substituer leurs fonctions par un rôle préventif sur la dégradation du glycocalyx et finalement accélérer le processus de réendothélialisation, 2002.

, De plus, nous avons mis en évidence qu'en l'absence de GAGs endogènes, suite à l'action de 4-Nitrophenyl-?-d-Xylopyranoside, la migration des HUVEC et la formation des réseaux vasculaires, 2015.

, Nous avons également démontré que le LMWF pouvait modifier l'expression des HS en modulant l'expression et l'activité de l'héparanase (HPSE), l'expression de l'exostosine-2 (EXT-2) et des syndécannes-1

, De plus, nous avons mis en évidence que les enzymes EXT-2 et HPSE, et que le SDC-4, sont impliqués dans l'effet pro-angiogénique du LMWF, puisque quand nous inhibons leurs expressions par des ARN interférents (small interfering RNA, siRNA), le pouvoir pro-angiogénique du fucoïdane est modulé negativement

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, Nous avons démontré par la suite qu'en absence de GAGs sur les HUVEC, le LMWF garde toujours son potentiel pro-angiogénique. Nous avons mis en évidence que l'exostosine-2 (EXT-2), l'héparanase (HPSE) et le syndécane-4 (SDC-4), sont impliqués dans l'effet proangiogénique du LMWF, puisque quand nous inhibons leurs expressions par ARN interférence, le pouvoir pro-angiogénique du LMWF est diminué. Nous avons démontré, dans le modèle d'hyperplasie intimale chez le rat, que le LMWF a un effet opposé sur l'expression des SDC. En effet, le LMWF induit l'expression du SDC-1 et diminue celle du SDC-4 dans la néo-intima. Nos données indiquent que l'EXT2, l'HPSE et le SDC-4 sont impliqués dans les effets pro-angiogéniques du LMWF, suggérant que les changements du métabolisme des HS liés à l'angiogenèse induite par le LMWF offrent la possibilité d'une nouvelle approche thérapeutique pour le traitement des maladies ischémiques. Syndecans and enzymes involved in heparan sulfate biosynthesis and degradation are implicated in pro-angiogenic effects of low molecular weight fucoidan. Induction of angiogenesis is a potential treatment for chronic ischemia. In this study we propose the analysis of pro-angiogenic treatment with fucoidan, sulfated polysaccharide from brown seaweeds, which act as glycosaminoglycans mimetics. Herein we used the low molecular weight fucoidan (LMWF), which presents a good affinity for pro-angiogenic factors (VEGF, SDF-1/CXCL12). The LMWF was mainly internalized through human vascular endothelial cell (HUVEC) clathrin-dependent endocytosis (in 2h) in which GAGs were partially involved. Our results showed that LMWF induced migration and angiogenesis in HUVEC. Interestingly, in a GAG-free HUVECs model, LMWF still kept a pro-angiogenic potential. In addition, we reported the implication of two heparan sulfate (HS) metabolism enzymes, exostosin-2 (EXT2) and heparanase (HPSE), and syndecan-4 (SDC-4) in LMWF induced angiogenesis. LMWF-treated and EXT2-or HPSE-siRNA-transfected cells shows that EXT2 or HPSE expression significantly affects the LMWF pro-angiogenic potential. In addition, LMWF increased SDC-1, but decreased SDC-4 expression. We studied the LMWF implication in SDC-1 and SDC-4 expression in rat model of intimal hyperplasia after balloon injury. Our results showed that LMWF treatment of injured artery increased SDC-1 expression, L'ischémie se définit par la réduction de la lumière d'un vaisseau, ce qui provoque dans les tissus une baisse du flux sanguin, et une hypoxie locale. Pour lutter contre l'ischémie, différentes thérapies pro-angiogéniques ont été développées afin de stimuler la formation de nouveaux vaisseaux à partir des vaisseaux préexistants

. Mots-clés, Syndécannes, fucoïdane, angiogenèse, cellules endothéliales, héparanase, p.12

I. Lvts, G. U1148, . Biothérapies, and . Glycoconjugués, Université Paris 13, UFR SMBH, 74 Rue Marcel Cachin 93 000