Low-molecular-weight fucoidan enhances the proangiogenic phenotype of endothelial progenitor cells (original) (raw)
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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.
Neoangiogenesis Induced by Progenitor Endothelial Cells: Effect of Fucoidan from Marine Algae
Cardiovascular & Hematological Agents in Medicinal Chemistry, 2007
Fucoidans --sulphated polysaccharides extracted from brown algae -could be beneficial in patients with ischemic diseases. Their antithrombotic and proangiogenic properties promote in animals, neovascularization and angiogenesis which prevent necrosis of ischemic tissue. In 1997, endothelial progenitor cells were first identified in human peripheral blood. They are recruited from bone marrow and contribute to neovascularization after ischemic injury. Mobilization of these cells in ischemic sites is an important step in new vessel formation. It is thought that the progenitors interact with endothelial cells, then extravasate and reach ischemic sites, where they proliferate and differentiate into new blood vessels. Although chemokines, cytokines and adhesion molecules are thought to be involved, the precise mechanism of progenitor mobilization is not fully understood. Recent studies suggest that stromal-derived factor 1 plays a critical role at several steps of progenitor mobilization. Given the role of proteoglycans within bone marrow, at the endothelium surface, and in growth factor and chemokine binding, fucoidans might influence the mobilization of endothelial progenitor cells and their incorporation in ischemic tissue. This review provides an update on circulating endothelial progenitors and their role in neovascularization. It focuses on recent advances in our understanding of interactions between these progenitor cells and exogenous sulphated polysaccharides, and their implications for understanding the fucoidan mechanism of action.
Fucoidan Inhibits Vascular Remodeling in Transplant Vasculopathy in Rat
Background: Fucoidan is a natural sulfated polysaccharide which exists mainly in the cell wall matrix of various species of brown seaweed. Various forms of fucoidan have also been recognized in some marine invertebrates such as sea urchins and sea cucumbers. Fucoidan inhibits the spread of cancerous cells by preventing the adhesion of tumor cells to the extracellular matrix in addition to inducing apoptosis, or programmed self-destruction, in human T-cells infected by T-cells leukemia virus type I (HTLV-1) which causes adult T-cell leukemia. The polysaccharide has also been shown to stimulate the phagocytic action of macrophages and synthesis of several immune cell types, which increases protection against infection. Fucoidan gives the immune system a big boost by enhancing phagocytosis. Additionally, it increases the number of mature white blood cells which are circulating in the body, thereby bolstering the first line of defense against infections and diseases. Moreover, fucoidan has anti-coagulant, anti-thrombotic, anti-inflammatory, antioxidant, anti-allergic, anti-tumor properties and also many others. Methods and Results: In this study, we investigated whether fucoidan is able to alleviate the vascular remodeling process triggered by immunological stimuli in rat allogenic aorta transplantation model, in addition to the evaluated potential mechanisms responsible for the observed effects. Our rat aorta transplantation model was subjected to intraperitoneal or oral treatment with fucoidan or placebo. The results of our study demonstrated that fucoidan inhibits endointimal hyperplasia formation and vascular modulation. In particular, intraperitoneal and oral administration of fucoidan reduced neointima formation in allografts retrieved 8 weeks after transplantation. Moreover, both treatments with fucoidan reduced the number of smooth muscle (SM) a-actin positive cells in intima and adventitia, decreased percentage of macrophages in intima and media, and increased the number of leukocytes in media of the allografts. Fucoidan treatments have also caused reduction in apoptosis in allograft intima and media. Conclusion: Through our study, we demonstrated the inhibitory effect of fucoidan on vascular remodeling in transplant vasculopathy within rats. Our study is the first report of the beneficial effects of fucoidan oral administration on this process, which may have important clinical implications and result in a better understanding of vascular remodeling. Keywords: fucoidan, transplant vasculopathy, vascular remodeling
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:
Mar. Drugs, 2024
Fucoidan is a class of multifunctional polysaccharides derived from marine organisms. Its unique and diversified physicochemical and chemical properties have qualified them for potential and promising pharmacological uses in human diseases, including inflammation, tumors, immunity disorders, kidney diseases, and diabetes. Physicochemical and chemical properties are the main contributors to these bioactivities. The previous literature has attributed such activities to its ability to target key enzymes and receptors involved in potential disease pathways, either directly or indirectly, where the anionic sulfate ester groups are mainly involved in these interactions. These findings also confirm the advantageous pharmacological uses of sulfated versus non-sulfated polysaccharides. The current review shall highlight the molecular targets of fucoidans, especially enzymes, and the subsequent responses via either the upregulation or downregulation of mediators’ expression in various tissue abnormalities. In addition, in silico studies will be applied to support the previous findings and show the significant contributors. The current review may help in understanding the molecular mechanisms of fucoidan. Also, the findings of this review may be utilized in the design of specific oligomers inspired by fucoidan with the purpose of treating life-threatening human diseases effectively.
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.
Biological effects of fucoidan isolated from Fucus vesiculosus on thrombosis and vascular cells
The Korean journal of hematology, 2010
Fucoidan is a highly sulfated glycosaminoglycan, which has a molecular structure similar to that of heparin. The antithrombotic effects of fucoidan in vitro have been widely reported, but its antithrombotic effects in vivo as well as its other biological properties in vitro have not been well investigated. This study investigated the effects and mechanism of fucoidan from Fucus vesiculosus on thrombosis both in vitro and in vivo. A ferric chloride-induced mouse carotid artery thrombosis model was used to determine the antithrombotic effects of fucoidan in vivo. Additionally, changes in the levels of proinflammatory cytokines and chemokines were examined in vascular cells treated with fucoidan. In vivo studies employing a ferric chloride-induced mouse carotid artery thrombosis model indicated that fucoidan had a stronger antithrombotic activity than heparin. Further, vascular cells treated with fucoidan demonstrated a decrease in proinflammatory cytokine and chemokine production as w...