Neoangiogenesis Induced by Progenitor Endothelial Cells: Effect of Fucoidan from Marine Algae (original) (raw)
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Low-molecular-weight fucoidan enhances the proangiogenic phenotype of endothelial progenitor cells
Biochemical Pharmacology, 2005
Endothelial progenitor cell (EPC) transplantation is a potential means of inducing neovascularization in vivo. However, the number of circulating EPC is relatively small, it may thus be necessary to enhance their proangiogenic properties ex vivo prior to injection in vivo. Fucoidan has previously been shown to potentiate in vitro tube formation by mature endothelial cells in the presence of basic fibroblast growth factor (FGF-2). We therefore examined whether fucoidan, alone or combined with FGF-2, could increase EPC proangiogenic potency in vitro. EPC exposure to 10 μg/ml fucoidan induced a proangiogenic phenotype, including cell proliferation (p < 0.01) and migration (p < 0.01); moreover, differentiation into vascular cords occurred in the presence of FGF-2 (p < 0.01). This latter effect correlated with upregulation of the cell-surface α6 integrin subunit of the laminin receptor (p < 0.05). Compared to untreated HUVEC, untreated EPC α6 expression and adhesion to laminin were enhanced two-fold. Fucoidan treatment further enhanced HUVEC but not EPC adhesion to laminin. These results show that fucoidan enhances the proangiogenic properties of EPC and suggest that ex vivo fucoidan preconditioning of EPC might lead to increased neovascularization when injected into ischemic tissues.
Therapeutic effect of fucoidan-stimulated endothelial colony-forming cells in peripheral ischemia
Journal of Thrombosis and Haemostasis, 2012
Background: Fucoidan, an antithrombotic polysaccharide, can induce endothelial colony-forming cells (ECFC) to adopt an angiogenic phenotype in vitro. Objectives: We evaluated the effect of fucoidan on vasculogenesis induced by ECFC in vivo. Methods: We used a murine hindlimb ischemia model to probe the synergic role of fucoidan-treatment and ECFC infusion during tissue repair. Results: We found that exposure of ECFC to fucoidan prior to their intravenous injection improved residual muscle blood flow and increased collateral vessel formation. Necrosis of ischemic tissue was significantly reduced on day 14, to 12.1% of the gastronecmius cross-sectional surface area compared with 40.1% in animals injected with untreated-ECFC. ECFC stimulation with fucoidan caused a rapid increase in cell adhesion to activated endothelium in flow conditions, and enhanced transendothelial extravasation. Fucoidan-stimulated ECFC were resistant to shear stresses of up to 21 dyn cm )2 . Direct binding assays showed strong interaction of fucoidan with displaceable binding sites on the ECFC membrane. Bolus intramuscular administration of fucoidan 1 day after surgery reduces rhabdomyolysis. Mice injected with fucoidan (15 mg kg )1 ) had significantly lower mean serum creatine phosphokinase (CPK) activity than control animals. This CPK reduction was correlated with muscle preservation against necrosis (P < 0.001). Conclusions:
Heparanase and Syndecan-4 Are Involved in Low Molecular Weight Fucoidan-Induced Angiogenesis
Marine drugs, 2015
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 expres...
Fucoidans: pro- or antiangiogenic agents?
Glycobiology, 2014
Sulfated polysaccharides of brown algae (fucoidans) attract great attention due to their high and strongly diversified biological activity. This review summarizes recent data on the structural variability of these polysaccharides and reports their anti- and proangiogenic properties. Recent publications have revealed that fucoidans isolated from different algal species may differ considerably in the structures of their backbones and branches, in both monosaccharide composition and sulfate content. It was found that the degree of sulfation significantly influences the biological properties of fucoidans. Additionally, fucoidan action in angiogenesis is highly dependent on molecular weight: antiangiogenic activity is connected with the high-molecular weight of polysaccharide molecules, whereas the low-molecular-weight fractions may act as proangiogenic agents. The influence of other fine structural details of fucoidans on angiogenesis remains to be established.
Marine Drugs, 2015
Low-molecular-weight fucoidan (LMWF) is a sulfated polysaccharide extracted from brown seaweed that presents antithrombotic and pro-angiogenic properties. However, its mechanism of action is not well-characterized. Here, we studied the effects of LMWF on cell signaling and whole genome expression in human umbilical vein endothelial cells and endothelial colony forming cells. We observed that LMWF and vascular endothelial growth factor had synergistic effects on cell signaling, and more interestingly that LMWF by itself, in the absence of other growth factors, was able to trigger the activation of the PI3K/AKT pathway, which plays a crucial role in angiogenesis and vasculogenesis. We also observed that the effects of LMWF on cell migration were PI3K/AKT-dependent and that LMWF modulated the expression of genes involved at different levels of the neovessel formation process, such as cell migration and cytoskeleton organization, cell mobilization and homing. This provides a better understanding of LMWF's mechanism of action and confirms that it could be an interesting therapeutic approach for vascular repair.
New therapeutics capable of favouring revascularization and thereby preventing tissue necrosis are needed for patients with critical ischemic disease. Several atherosclerotic diseases such as peripheral and coronary arterial disease, as well as traumatic injury, can lead to arterial occlusion or compression. Downstream tissues become ischemic and, if blood circulation is not quickly re-established, necrosis occurs with a risk of physical or functional loss. Fucoidans, marine sulphated polysaccharides with venous and arterial antithrombotic properties in experimental animal models, might be beneficial for patients with ischemic diseases. In animals, fucoidans promote the formation of new blood vessels, thereby preventing necrosis of ischemic tissue. Low molecular weight fucoidan has greater antithrombotic/haemorrhagic risk ratio potential than heparin, a well-known sulphated polysaccharide used in the prevention of thrombosis. Owing to their ionic structure, fucoidans mimic some prop...
Marine Drugs, 2016
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.
Drug Delivery and Translational Research, 2013
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Therapeutic Potential of Fucoidan in Myocardial Ischemia
Journal of Cardiovascular Pharmacology, 2011
Fucoidan, a sulfated polysaccharide extracted from brown seaweed, is a candidate for the treatment of ischemic diseases. The aim of this study was to measure the therapeutic potential of fucoidan in a rat model of myocardial ischemiareperfusion injury. Forty rats were submitted to myocardial ischemia-reperfusion injury by transient occlusion of the left coronary artery. Rats were then randomized into 2 groups: fucoidan (5 mg/kg, intramuscularly; n = 20) or control (saline intramuscularly; n = 20) was administered 1 hour before injury and daily thereafter for 1 month. At 1 month, plasma levels of stromal cellderived factor-1a (SDF-1a) were assessed by enzyme-linked immunosorbent assay kit. Hearts were evaluated by histoimmunochemistry. Fucoidan induced significant antifibrotic effects, reducing the infarct scar size by almost 30% on Sirius red-stained sections (9.45% ± 4.27% vs. 13% ± 5.67% in controls; P = 0.03). Vascular density in the fucoidan group (a-actin, RECA-1, or lectin BS1 stained) was increased by 40% (2.18 ± 0.79 mm 2 vs. 1.49 ± 0.42 mm 2 in controls ·200; P = 0.001). Plasma SDF-1a at 1 month was not significantly different between the 2 groups. However, increased immunostaining density of SDF-1a and vascular endothelial growth factor in fibrotic ischemic tissues was observed in fucoidan-treated animals versus controls. In conclusion, fucoidan enhanced tissue repair in myocardial ischemiareperfusion by promoting revascularization (in situ vascular endothelial growth factor and SDF-1a overexpression) and limiting fibrosis. Consequently, fucoidan may be useful for myocardial ischemic patients.